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School of Medicine

Research projects and information for prospective

students 2015

Honours, Masters and PHD

CRICOS Provider Code: 00113B

School of Medicine Faculty of Health Geelong Waurn Ponds, Locked Bag 20000, Geelong, VIC 3220 Tel 03 5227 5740 Fax 03 5227 5555 [email protected] www.deakin.edu.au

Table of Contents

Contents INFORMATION FOR PROSPECTIVE HONOURS STUDENTS ................................................................................................. 3

AN OVERVIEW OF THE HONOURS PROGRAM H413 .......................................................................................................................... 3 ENTRANCE REQUIREMENTS ......................................................................................................................................................... 3 COURSE STRUCTURE OF H413 .................................................................................................................................................... 3 HONOURS SCHOLARSHIPS ........................................................................................................................................................... 4 CONTACT DETAILS ..................................................................................................................................................................... 4 APPLYING FOR HONOURS ........................................................................................................................................................... 4 2015 HONOURS PROJECT PREFERENCE FORM................................................................................................................................ 6

DOCTOR OF PHILOSOPHY AND MASTER BY RESEARCH ..................................................................................................... 7

APPLYING ................................................................................................................................................................................ 7

INDEX OF PROJECTS FOR 2015 .......................................................................................................................................... 8

METABOLISM & MUSCLE BIOLOGY .............................................................................................................................................. 8 1. Oxidative stress and the matrix: implications for muscle repair .............................................................................. 8 2. Oxidative stress and the matrix: disrupting metabolism in exercise & diabetes ...................................................... 9 3. The role of class IIa histone deacetylases in diseases of defective oxidative metabolism ..................................... 10 4. microRNA and the development of cardiac hypertrophy ....................................................................................... 11 5. The implications of extracellular networks in obesity and type 2 diabetes ............................................................ 12 6. The role of metformin in β-cell regeneration in diabetes ....................................................................................... 13 7. Discovery of new targets for the treatment of diabetes ........................................................................................ 14 8. Epigenetic determinants of obesity in Psammomys obesus ................................................................................... 15 9. Discovering a new treatment for fatty liver disease .............................................................................................. 16 10. Effects of reduced Selenoprotein S (SEPS1) in the mdx dystrophic mouse ......................................................... 17

INFECTION & IMMUNITY........................................................................................................................................................... 18 11. Modulating Influenza virus immunity using miRNAs ......................................................................................... 18 12. Understanding the role of CISH in influenza virus immunity .............................................................................. 19 13. When is an infectious microorganism truly dead? ............................................................................................. 20 14. Control of early blood and immune cell development: role of Ikaros transcription factors ............................... 21 15. Development of miRNA-based early detection technology for emerging infectious diseases ........................... 22 16. Development of novel anti-viral therapeutics against MERS-CoV ..................................................................... 23 17. Development of therapeutic and diagnostic antibodies .................................................................................... 24 18. An investigation of T regulatory cell stability in early life allergic disease ......................................................... 25 19. The relationship between nasal colonisation and allergic disease in infants ..................................................... 26 20. A population based investigation of the early life origins of cardiovascular disease ......................................... 27 21. Dietary fermentable fibre, short chain fatty acids and allergic disease ............................................................. 28 22. Genome engineering to control Avian Influenza Virus with RNA interference................................................... 29 23. Molecular characterization of viral pathogenicity: effect of NDV fusion protein glycosylation ......................... 30 24. An active genetic factor in milk? Can mother still be controlling baby's immune genes? ................................. 31 25. How will urbanisation impact disease emergence? ........................................................................................... 32 26. Engineering the chicken genome to fight food-poisoning bacteria ................................................................... 33 27. Programming cell death: characterisation of death receptor pathways in bats................................................ 34 28. Cytokine receptor signaling in bats .................................................................................................................... 35 29. Mosquito and virus: genomics arms race........................................................................................................... 36 30. Is the pigeon crop the avian mammary gland? .................................................................................................. 37 31. Understanding the role of NOX2 in influenza-induced hypercytokinemia in a knockout chicken cell line ......... 38 32. The development of host-derived antivirals for emerging infectious disease threats ....................................... 39 33. Role of Zinc-alpha-2-glycoprotein (ZAG): Relationship between Disease and ZAG Glycosylation ..................... 40 34. Dissecting the viral entry using super-resolution microscopy and electron microscopy .................................... 41 35. Assembly and maturation of human immunodeficiency virus type 1 ................................................................ 42 36. How does human immunodeficiency viruses type 1 diversify? .......................................................................... 43 37. Device and biofilm infections ............................................................................................................................. 44



38. Mycobacteria ulcerans flesh eating bacteria ..................................................................................................... 45 39. Infective endocarditis in the 21st century .......................................................................................................... 46 40. Dissecting how rhoptry proteins help malaria parasites secure their survival in host red blood cells ............... 47 41. Targeting the Achilles’ heel of the malaria parasite .......................................................................................... 48

MENTAL HEALTH & NEUROSCIENCE ........................................................................................................................................... 49 42. The relationship between maternal stress during pregnancy and offspring behaviour and mental health ...... 49 43. Clinical factors involved in the effects of N-acetyl cysteine treatment in depression ........................................ 50 44. Clinical factors involved in the effects of N-acetyl cysteine treatment in autism ............................................... 51 45. Novel therapies for Huntington’s disease: targeting nervous system and metabolic dysfunction .................... 52 46. Reintroducing good old friend: insulin like growth factor-1 protection against neuronal insults ...................... 53 47. Later life mood, anxiety and personality disorders and treatment .................................................................... 54 48. Stressed, sick and sad; interactions between inflammation and mood. ............................................................ 55 49. Qualitative analysis of the effects of N-acetyl cysteine treatment in unipolar depression ................................ 56 50. Evaluating the relationship between anxiety symptoms and dietary intake those with depression ................. 57 51. Validation of a brief diet quality screening tool ................................................................................................. 58

DEVELOPMENT & CANCER ........................................................................................................................................................ 59 52. The role of C-type natriuretic peptide in ovary and placenta ............................................................................. 59 53. Role of cytokine receptor signaling in development and disease ....................................................................... 60 54. Generation of induced pluripotent stem cells .................................................................................................... 61 55. Translational research of tailored neoadjuvant chemotherapy for newly diagnosed breast cancer ................. 62 56. Evaluation of new breast cancer drug Palbociclib in combination with radiation therapy ................................ 63 57. Potential therapeutic use for a novel histone deacetylase inhibitor in paediatric solid tumours ...................... 64 58. Genetic of tooth development in zebrfaih .......................................................................................................... 65 59. The fate of Mesenchymal Stem Cells: how to get bone in zebrafish? ................................................................ 66 60. Microfluidics based circulating tumor cell (CTC) capture and analysis from patient samples ........................... 67 61. Fat, muscle and cancer ....................................................................................................................................... 68 62. Developing aptamers into diagnostic tools ........................................................................................................ 69 63. Targeting cancer with chemical antibodies ....................................................................................................... 70 64. The quest for a biomarker of cancer cachexia ................................................................................................... 71 65. Free living activity assessment of patients with cancer cachexia ...................................................................... 72 66. Novel treatments of cancer cachexia ................................................................................................................. 73 67. The role of free radicals in the development of cancer cachexia ....................................................................... 74 68. Chemokine signalling, bone marrow derived endothelial progenitor cells (EPCs) and cancer. .......................... 75 69. Identification and functional validation of downstream targets of cancer microRNAs. .................................... 76 70. Specific Targeting of MicroRNAs as a Novel Anti-Cancer Therapy. .................................................................... 77

NUTRITION, BONE HEALTH ....................................................................................................................................................... 78 71. Can histone deacetylase inhibitors stimulate bone formation? ......................................................................... 78 72. Identifying the role of miRNA in the development and regulation of inflammatory rheumatic diseases .......... 79 73. Childhood asthma and the risk of fracture ......................................................................................................... 80 74. Sarcopenia and nutritional risk, falls and functional mobility ............................................................................ 81 75. The epidemiology of limb fractures .................................................................................................................... 82 76. Food outlet space allocated for fruit and vegetables and health status in Australian farmers? ....................... 83 77. Bone mineral density in monoclonal gammopathy of uncertain significance (MGUS) ...................................... 84 78. Determining trends in diet quality over the long term ....................................................................................... 85 79. Are medical students healthy? An assessment of chronic disease factor prevalence ........................................ 86

OTHER .................................................................................................................................................................................. 87 80. Action of Dopamine and antipsychotics on bone formation, in zebrafish.......................................................... 87 81. Cage, barn or free range? Which system has the happiest chicken? ................................................................. 88 82. Ageing, chronic disease and quality of life ......................................................................................................... 89 83. Modifiable risk factors for chronic disease: a population-based study .............................................................. 90 84. Are there gender differences in food consumption patterns by individuals with major depression .................. 91 85. Does participation in the control group of a health intervention prompt changes in health behaviour? .......... 92



Information for prospective Honours students

An overview of the Honours program H413 The Honours program in the School of Medicine is designed to build upon the skills and knowledge obtained from the completion of a three year undergraduate degree. The program aims to provide students with the opportunity to pursue an independent investigative research project in the areas of health and medicine along with relevant course work. This will enable students to expand their depth of knowledge in their chosen research area and provide a suitable qualification for entry into a higher degree by research program (Masters or PhD). The School of Medicine program is a Type A Honours Degree, leading to award of a Bachelor of Health and Medical Sciences (Honours) (course code H413). This program, which comprises both coursework units and a research thesis, is undertaken over one year full-time. Each student is allocated a primary research supervisor and in some circumstances a co-supervisor.

Entrance requirements To be eligible for entry into the Bachelor of Health and Medical Science (Honours), students must have completed an accredited undergraduate degree in the broad area of health and medical science (of at least three-years’ length) in a discipline related to the area of their research project. Students will require a mid-credit (>65%) average for the final full-time year (or part-time equivalent) of undergraduate study to be eligible for selection. Entry will also be determined by the availability of supervisors and resources.* Bachelor of Medicine Bachelor of Surgery (H311) students who do not meet the above entry requirement, and wish to apply will require a minimum GAMSAT score of 60, and have successfully completed a minimum of 8 credit points of the Bachelor of Medicine Bachelor of Surgery course. Entry into H413 for Bachelor of Medicine Bachelor of Surgery (H311) students will be available at the end of the first, second or third year of the course and will be a competitive process. Entry will also be determined by the availability of supervisors and resources.* *NB: Course entry requirements are subject to approval.

Course Structure of H413 The course comprises three Units, worth a total of eight credit points to be taken over one year of full-time study. The requirements include: an independent research project/thesis worth four credit points conducted under the supervision of the nominated supervisor for that project, a two credit point unit in research methods, and a two credit point unit in developing research skills in health and medical sciences. The course will be structured in the following way:

HMH401: Developing Research Skills 2 credit points (Trimester 1)

HBS400: Research Methods 2 credit points (Trimester 1)

HMH402: Honours Research Project 4 credit points (Trimester 2)

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School of Medicine Faculty of Health Geelong Waurn Ponds, Locked Bag, 20000, VIC 3220 Tel 03 5227 5740 Fax 03 5227 55555 [email protected] www.deakin.edu.au

HMH401: This Unit will provide you with a thorough understanding of your research field through the generation of a research proposal whilst at the same time helping you to develop skills essential to research, including online literature searching, presentation skills and critical analysis of literature. Assessment involves the development of a research proposal, the completion of a literature review and an oral presentation of the research findings prior to submission of the thesis.

HBS400: This is a Faculty-wide Unit comprised of a series of modules, in which the students must complete a required number of modules. Students select modules that are the most relevant to their project and in areas in which they require support. All modules are completed and assessed in Trimester 1.

HMH402: This Unit involves the implementation of the research project. While the enrolment is in Trimester 2, students will actually commence their research project in Trimester 1. The assessment for this Unit is writing up the research in a thesis format that includes a literature review, research methodologies, research results and a discussion of the findings. The literature review (which is undertaken as part of HMH401) will be only assessed in relation to the relevance to the project and the hypothesis and aims.

• Developing Research Skills Trimester 1 2 credit points

• Research Methods Trimester 1 2 credit points

• Research Project/Thesis Trimester 2 4 credit points

The Honours year is an exciting year because it provides the first real opportunity to get a feel for research and students develop a wide range of research and problem-solving skills. However, students should be aware that this year is a challenging and demanding year, involving at least 35 hours per week of study and/or research work.

Honours Scholarships

Commencing Honours students are eligible to apply for merit-based Scholarships to the value of $1,000 and $2,000.

Contact details For further information please contact the Honours coordinator: Assoc Prof John Stambas Phone: (03) 52275740 Fax: (03)52275555 Email: [email protected]

Applying for Honours To apply for Honours in the School of Medicine please follow the steps below: 1. Select a research project Examine the list of research projects that the school is offering for 2015. For those projects that you are interested in, you must personally contact the named supervisor to discuss the proposed project. The

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mailto:[email protected]

supervisors contact details are provided together with the project description. This will enable you to gauge whether the research project aligns with your career goals, and enables the supervisor to establish whether you have the appropriate academic background to undertake and complete the research project. 2. Complete the project preference form This form is provided in this booklet. Either hand in to the School of Medicine reception staff, or alternatively email [email protected] or post to Student Experience Team (School of Medicine, Deakin University, Locked Bag 20000 Geelong, Vic. 3220) by November 14, 2014. This form MUST be filled out so that projects can be allocated to students based on the criteria outlined below. 3. Submit an on-line application All prospective honours students MUST also apply directly to Deakin University. Submit an online application at http://applicantportal.deakin.edu.au/connect/webconnect. Closing dates for applications is November 14, 2014.

• You will need to register as a user in order to apply. Select the ‘Register’ link to activate a username and password to gain entry to the online application. NOTE: Current Deakin students – your Deakin username and password will not gain you access to the online application.

• Complete all of the questions on the online application. NOTE: Referee details are not required • Complete the final step ONLY if your undergraduate studies were NOT undertaken at Deakin

University. This final step requires applicants to upload scanned and certified copies of their University academic transcript(s).

4. Project allocation Students will be allocated a project based on a combination of student preferences, supervisor’s student preferences and a mid-credit (>65%) average for the 3rd year or equivalent of undergraduate study. Successful candidates will be advised of their offer during end Nov-early Dec 2014. The projects on offer within the School of Medicine reflect the expertise and research that is currently undertaken by the prospective supervisors at Deakin and at our affiliate institutes. It must be noted that due to the nature of research, the focus and direction of a research group may change over time and the final project may not necessarily be exactly as described. Please refer to the website for any further information on Honours in the School of Medicine: http://www.deakin.edu.au/hmnbs/medicine/research/research-projects

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http://applicantportal.deakin.edu.au/connect/webconnect

http://www.deakin.edu.au/hmnbs/medicine/research/research-projects

2015 Honours Project Preference Form Your name: Address: Postcode Contact Phone Number: Email: Deakin student ID: Applicants are advised that allocation to research projects is a competitive process and an applicant cannot be assured of being assigned to their choice of research projects. Please nominate below three preferences, in order, for an Honours project (and supervisor) for 2015 from the list of projects on offer. 1st preference - Project number: Project title: Supervisor: Have you personally spoken with the supervisor about the project? Yes No 2nd preference - Project number: Project title: Supervisor: Have you personally spoken with the supervisor about the project? Yes No 3rd preference - Project number: Project title: Supervisor: Have you personally spoken with the supervisor about the project? Yes No If you are NOT offered one of the above projects would you consider an offer of an Honours project in a related area? Yes No Please hand this form in to the School of Medicine reception staff, or alternatively email [email protected] or post to Student Experience Team (School of Medicine, Deakin University, Locked Bag 20000, Geelong, Vic 3220) by November 14, 2014 for timely applications. In some circumstances, late applications will be considered depending on availability of appropriate supervisors, projects and places up until January 31, 2015.

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mailto:[email protected]

Doctor of Philosophy and Master by Research The key to entry (besides meeting entry qualifications) into a PhD or Masters by Research program is the support of a School of Medicine staff member to supervise you. It is essential, therefore, that you discuss your application for one of the listed projects with the relevant supervisor(s) prior to applying. Note the application form requires an applicant to provide a one page outline of their proposed research program.

Applying Applications for candidature are accepted at any time; however for applicants seeking scholarships please note the appropriate closing dates shown below. With the support of a supervisor, submit an application. The application and scholarship process for Australian and New Zealand Citizens and Australian Permanent Residents can be found at: http://www.deakin.edu.au/future-students/research/how-to-apply.php and http://www.deakin.edu.au/future-students/research/scholarships/apa-dupr-scholarship-information.php. Applications for scholarships close at the end of October each year. The application and scholarship process for International applicants can be found at: www.deakin.edu.au/internationalisation/hdr. Applications for scholarships from International students close at the end of July each year.

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http://www.deakin.edu.au/future-students/research/how-to-apply.php

http://www.deakin.edu.au/future-students/research/scholarships/apa-dupr-scholarship-information.php

http://www.deakin.edu.au/internationalisation/hdr

Index of projects for 2015

Metabolism & Muscle Biology

1. Oxidative stress and the matrix: implications for muscle repair Supervisor/s: Nicole Stupka Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: The connective tissue (extracellular matrix) that surrounds muscle fibres and their progenitor cells is more than a scaffold to provide structural support; it is a dynamic tissue that sends signals to muscle fibres and progenitor cells to regulate all aspects of cell behaviour, including inflammation and repair following injury. For optimal skeletal muscle health, connective tissue composition and remodelling of its constituent components need to be carefully regulated. Oxidative stress and pro-inflammatory cytokines activate signalling pathways which disrupt the protein composition of the extracellular matrix leading to fibrosis and loss of contractile function.

Duchenne muscular is a fatal X-linked genetic disease caused a mutation in the DYSTROPHIN gene. The functional protein is not expressed rendering muscles vulnerable to injury leading to degeneration, muscle fibre loss due to ineffective repair, expansion of the extracellular matrix and fibrosis. Excess oxidative stress and pro-inflammatory cytokines in dystrophic muscles contribute to disease pathology and accelerate the functional decline.

We are investigating how oxidative stress and inflammation affect the composition, remodelling and expansion of the extracellular matrix and the downstream consequences for skeletal muscle repair and function in dystrophy. It is evident that to ameliorate the pathology of Duchenne muscular dystrophy, the dysregulation of the extracellular matrix must be targeted. Therefore, we are characterising the function of some novel candidate proteins, including the extracellular proteoglycan versican, ADAMTS proteases which remodel versican, and the antioxidant protein selenoprotein S (SEPS1), which has been implicated in inflammation and oxidative stress.

Using cell culture and transgenic mouse models relevant to Duchenne muscular dystrophy, this Project will examine the roles of those genes in the context of inflammation, regeneration and muscle function.

Contact supervisor: Dr. Nicole Stupka (Deakin Medical School): [email protected] 5227 1360 Suitable for: Honours or PhD This project is subject to final approvals.

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2. Oxidative stress and the matrix: disrupting metabolism in exercise & diabetes Supervisor/s: Nicole Stupka Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Obesity due to a nutrient excess impairs the action of insulin, a key hormone in controlling metabolism, and can result in the development of type 2 diabetes. Inside the cell, excess of nutrients, lipids in particular, activate intracellular oxidative and ER stress and pro-inflammatory responses impairing insulin sensitivity and compromising mitochondrial function. Exercise also increases oxidative, ER and inflammatory stress, however it is protective against insulin resistance and improves mitochondrial function because the stress is transient. A stress response protein of particular interest is selenoprotein S (SEPS1), as it has antioxidant, anti-ER stress and anti-inflammatory properties and has been linked to inflammatory diseases in humans.

Outside the cell, there is emerging evidence that excess nutrients disrupt the surrounding connective tissue (extracellular matrix) dysregulating inflammatory responses and exacerbating oxidative stress. The extracellular matrix does more than just provide structural support - it is bioactive and transmits signals to modulate all aspects of cell behaviour. It consists of various structural proteins and the enzymes which cleave them, and this remodelling process is vital in regulating cell function. The specific aspect of connective tissue remodelling we are interested in is the cleavage of a major component of the extracellular matrix called “versican” by ADAMTS enzymes. As the published literature and our own data show that obesity and a high fat diet alter the expression levels of these extracellular matrix proteins in adipose tissue, liver and skeletal muscle.

Using cell culture and transgenic mouse models relevant to insulin resistance and endurance exercise, this Project will examine the roles of SEPS1, versican and ADAMTS enzymes in the context of oxidative and ER stress, inflammation and metabolism.

Contact supervisor: Dr. Nicole Stupka (Deakin Medical School): [email protected] 5227 1360 Suitable for: Honours or PhD This project is subject to final approvals.

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3. The role of class IIa histone deacetylases in diseases of defective oxidative metabolism Supervisor/s: Sean McGee Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Defects in oxidative metabolism characterise a number of chronic diseases, including diabetes, neurodegenerative disorders, cancer and cardiovascular disease. The class IIa histone deactylases (HDACs) are transcriptional repressors through the epigenetic regulation of chromatin structure. We have identified the class IIa HDACs are critical regulators of skeletal muscle oxidative metabolism in type 2 diabetes through the control of oxidative enzyme gene expression. Bioinformatics analyses suggest that the class IIa HDACs could be involved in numerous diseases characterised by defective oxidative metabolism. However this has yet to be verified experimentally. Furthermore, it is unclear how the class IIa HDACs are regulated to subsequently impair oxidative metabolism. Using a multidisciplinary approach that including bioinformatics, molecular biology and physiological outcome measures in both in vitro and in vivo model systems, this project will seek to establish whether the class IIa HDACs are common contributors to the development of a number of diseases that have their origins in defective oxidative metabolism. Data generated from these experiments could lead to the development of therapeutics designed to enhance oxidative enzyme gene expression and oxidative metabolic flux for the treatment of diverse diseases such as diabetes, neurodegenerative disorders, cancer and cardiovascular disease.

Contact supervisor: Dr. Sean McGee (Deakin Medical School): [email protected] 03 5227 2519 Suitable for: Honours or PhD This project is subject to final approvals.

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4. microRNA and the development of cardiac hypertrophy Supervisor/s: Paul Lewandowski, Fadi Charchar Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Cardiac hypertrophy is a potential life threatening disease. There is a need to understand the various mechanisms and pathways involved in the development of the condition to find effective means of diagnosis, prevention and treatment. The disease is a concern as complications due to end organ damage resulting from chronic exposure to increased blood pressure can be adverse and fatal. To study cardiac hypertrophy A/Prof. Lewandowski’s laboratory has developed novel cell culture and rat models of the condition that they employ to study the development of the disease and its treatment. Interestingly it would seem that select microRNA sequences maybe responsible for regulating the development of heart size and most likely responsible for cardiac hypertrophy. The current project will investigate the genetic and environmental triggers that may contribute to the modulation of heart cell size and development of cardiac hypertrophy. Included in these triggers are changes to diet and nutrient intake.

This project will provide students with the opportunity to learn cell culture techniques, animal surgical techniques and skills needed to run a dietary trial. In addition the project also incorporates gene expression analysis, protein electrophoresis & immunoblotting, biochemical analysis, enzymatic analysis and histological analysis.

Contact supervisor: Assoc. Prof. Paul Lewandowski (Deakin Medical School): [email protected] 03 52271111 Suitable for: Honours or PhD

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5. The implications of extracellular networks in obesity and type 2 diabetes Supervisor/s: Daniel McCulloch, Kathryn Aston-Mourney, Sean McGee, Nicole Stupka Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Obesity and type 2 diabetes (T2D) is a global health problem and major economic burden in developed countries. Current therapies include insulin-sensitising drugs complemented with diet and exercise regimens; however a significant amount of patients develop cardiovascular disease, leading to high rates of morbidity and death. Recent genome-wide associations screens, alongside studies carried out at the School of Medicine's Metabolic Research Unit (MRU) have identified several genes as strong predictors of T2D susceptibility. Among those are genes encoding for extracellular remodelling enzymes called "ADAMTS". We have several ADAMTS knockout mouse lines at the MRU that we would like to test for their susceptibility to insulin-resistance on a high-fat diet, as a follow-up to those screens identifying these genes as important in the development of T2D. This project will utilise mouse models alongside echocardiography, serum glucose and cytokine analyses, gene and protein expression, and muscle function to assess the potential mechanisms by which extracellular ADAMTS enzymes mediate insulin-resistance and the development of T2D. Identifying those mechanisms may lead to the discovery of new drug targets that improve treatment efficacy for T2D patients.

Contact supervisor: Dr. Daniel McCulloch (Deakin Medical School): [email protected] 52272838 Suitable for: Honours This project is subject to final approvals.

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6. The role of metformin in β-cell regeneration in diabetes Supervisor/s: Kathryn Aston-Mourney, Yann Gibert Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Diabetes is one of the major health burdens facing the world today. Both type 1 and type 2 diabetes are characterised by a complete or partial loss of the insulin producing cells in the pancreas (β-cells). Human β-cells have a very limited capacity for regeneration however zebrafish are able to completely regenerate their pancreas. Additionally, new evidence suggests that the diabetes drug metformin may be able to stimulate β-cell regeneration.

This project will use a zebrafish model of pancreas ablation and regeneration and determine whether metformin is able to accelerate or increase the regenerative capacity. Following this, next generation sequencing carried out to determine the gene pathways involved in this process. Identification of the pathways involved in β-cell regeneration may lead to novel drug targets and eventually a way in which the human pancreas can be regenerated thereby curing diabetes.

This project will involve the following: • Zebrafish breeding and treatment • Immunohistochemistry • In situ hybridization • Analysis of cell death • Analysis of cell proliferation • RNA extraction and purification • Next generation sequencing Contact supervisor: Dr. Kathryn Aston-Mourney (Deakin Medical School): [email protected] 52272977 Suitable for: Honours

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7. Discovery of new targets for the treatment of diabetes Supervisor/s: Kathryn Aston-Mourney, Ken Walder Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Type 2 diabetes is one of the major health burdens facing the world today. Diabetes is characterised by failure of the insulin producing cells in the pancreas (β-cells). β-cell failure is progressive, with patients requiring additional medications over time and eventually insulin injections. Current diabetes treatments cannot stop or slow the progression of β-cell failure; therefore it is vital that we obtain a better understanding of how β-cell failure occurs and how it could be targeted by new treatments.

We aim to characterize the role of several genes identified from next generation sequencing experiments in a cell model of β-cell failure. This will provide novel information and targets for the development of new drugs to treat type 2 diabetes.

The project will involve the following: • Genetic manipulation of cells • Analysis of insulin secretion • Analysis of cell death • RNA extraction and purification • Real-time PCR • Western blotting • ELISA Contact supervisor: Dr. Kathryn Aston-Mourney (Deakin Medical School): [email protected] 52272977 Suitable for: Honours

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8. Epigenetic determinants of obesity in Psammomys obesus Supervisor/s: Ken Walder, Sean McGee Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: There has been much recent interest in the role of the maternal diet during pregnancy on susceptibility to metabolic disease in the offspring. Several recent studies have shown that changes in the transcriptional activity of DNA can produce sustained metabolic adaptations. Within key tissues such as hypothalamus, adipose tissue, skeletal muscle and liver, metabolic function in offspring can be affected by alteration to the maternal diet via modulation of DNA methylation and histone acetylation, which suggests epigenetic programming. In this project, we will utilize a unique animal model of metabolic disease, the Israeli sand rat, to investigate how changing the maternal diet affects metabolic function in the offspring, and we will use cutting edge methods to assess genome wide methylation and gene expression in the hypothalamus. These studies will provide new information on the effects of maternal diet on long term consequences for the offspring, and will highlight key genomic regions, genes and pathways that mediate these effects.

Contact supervisor: Prof. Ken Walder (Deakin Medical School): [email protected] 5227 2883 Suitable for: Honours or PhD This project is subject to final approvals.

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9. Discovering a new treatment for fatty liver disease Supervisor/s: Ken Walder, Briana Spolding Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the developed world, and is linked to the Metabolic Syndrome (including obesity and type 2 diabetes). NAFLD is present in up to 80% of obese subjects, and is characterised by a pathological accumulation of fat in the liver, that may be associated with inflammation (non-alcoholic steatohepatitis). NAFLD can affect liver function, and is a risk factor for developing cirrhosis of the liver and hepatocellular carcinoma, both of which can result in death. Current treatments are based on management of co-morbidities, and don’t address the underlying liver pathology. We have discovered that an experimental diabetes drug currently in clinical trials improved liver function in diabetes patients. In this project we will use an animal model of fatty liver disease and measure the precise effects of this new drug on the liver, and investigate the mechanism(s) by whioch the drug is working. This will highlight the potential for treating obesity, type 2 diabetes and fatty liver disease simultaneously, and pave the way for clinical trials to improve patient outcomes.

Contact supervisor: Prof. Ken Walder (Deakin Medical School): [email protected] 5227 2883 Suitable for: Honours

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10. Effects of reduced Selenoprotein S (SEPS1) in the mdx dystrophic mouse Supervisor/s: Craig Wright, Nicole Stukpa Location: School of Exercise and Nutrition Sciences, Deakin University, Waurn Ponds Campus Project description: In humans, gene polymorphisms in Selenoprotein S are associated with inflammation. SEPS1 is highly expressed in skeletal muscle and is protective against inflammation, oxidative and ER stress. Excess inflammation and cellular stress are hallmarks of chronic muscle wasting diseases, including Duchenne Muscular Dystrophy (DMD), and lead to compromised repair and poor contractile function. Here, we propose to investigate the role of a reduction in SEPS1 expression in skeletal muscle inflammation, repair and muscle function in SEPS1 heterozygous knockout mdx dystrophic mice. The aims of this study are to investigate the role of SEPS1 in systemic and skeletal muscle inflammation in order to elucidate a role for SEPS1 in skeletal muscle repair and inflammation. This could lead to the development of novel therapeutric approaches for muscular dystrophy. Prof Sof Adrinkopoulos (Austin Hospital, The University of Melbourne) has demonstrated that SEPS1 heterozygous knockout mice (SEPS1-/+) have reduced SEPS1 protein expression compared to wild-type litter-mates in peripheral tissues, including skeletal muscle. Therefore, cross breeding a SEPS1(-/+) with an mdx dystrophic mouse will produce male SEPS1-/+ mdx dystrophic pups and dystrophic litter mate controls. Specifically, body composition, metabolism and spontaneous physical activity, whole body strength and ex vivo contractile function testing on isolated hindlimb muscles. End point measures will include gene and protein anaylsis from peripheral tissues including skeletal muscle and bone marrow derived cells in cell culture using molecular biology techniques. Contact supervisor: Dr. Craig Wright (School of Exercise and Nutrition Sciences): [email protected] 03 5247 9266 Suitable for: Honours This project is subject to final approvals.

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Infection & Immunity

11. Modulating Influenza virus immunity using miRNAs Supervisor/s: John Stambas, Leonard Izzard Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: In 2009, the emergence of pandemic swine-origin H1N1 influenza virus and the recent H7N9 outbreaks in China have highlighted to the scientific community and to governments worldwide, the ongoing, unpredictable and very real threat influenza viruses pose to human health. Improving current live vaccine strategies is critical to ensure adequate protection for future pandemics. This project will use cutting edge technology, known as reverse genetics to insert microRNA (miRNA) sequences into influenza viruses in order to regulate the physiological development of immune cell populations following infection. MiRNA are short RNA molecules ~18-22 nucleotides in length that regulate expression of many genes at a post-transcriptional level by inhibiting the translation of messenger RNA (mRNA) to protein. They achieve this by binding to mRNA through the RISC complex causing either degradation of the mRNA (if a perfect complementary sequence) or inhibition (if an imperfect complementary sequence). This regulation of gene expression is believed to be involved in the development and physiology of all eukaryotes. By inserting our miRNAs of interest (mir-21, mir-146a and mir-150) into the virus itself for delivery to the host, we aim to more efficiently eliminate virus following infection through the deliberate expansion of specific immune cell populations. Contact supervisor: Assoc. Prof. John Stambas (Deakin Medical School): [email protected] 52275740 Suitable for: Honours or PhD

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12. Understanding the role of CISH in influenza virus immunity Supervisor/s: John Stambas, Alister Ward Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: The impact of influenza virus infection is an ongoing major public health concern. Significant morbidity and mortality is associated with infection, especially in susceptible populations such as the very young and elderly. In has been suggested that each year, influenza virus infection in Australia results in approximately 310,000 general practitioner consultations, 18,400 hospitalisations and a 115 million dollar burden to the Australian healthcare system. Understanding the mechanisms that drive immunity and protection from virus infection is critical for the development of novel intervention strategies to improve epidemic and pandemic preparedness. Importantly genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the human CISH (cytokine-inducible SH2-containing protein) gene associated with increased susceptibility to a number of infectious agents, including malaria, invasive bacteria and certain viruses. CISH is a member of the suppressor of cytokine signalling (SOCS) family of negative regulators. It is induced by a number of important haematopoietic cytokines, including erythropoietin and various interleukins, and subsequently inhibits their signalling in vitro. However, understanding of the in vivo function of CISH remains limited, especially following virus infection. Utilising a newly-developed Cish knockout mouse and the well characterised influenza mouse model we aim to determine the role of CISH following influenza virus infection.

Contact supervisor: Assoc. Prof. John Stambas (Deakin Medical School): [email protected] 52275740 Suitable for: Honours This project is subject to final approvals.

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13. When is an infectious microorganism truly dead? Supervisor/s: Andrew Leis, Johnson Mak, John Stambas, Sean Pham Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Highly pathogenic bacteria and viruses pose a serious and increasing risk to human health. We wish to determine the most important question: “Is the infectious agent capable of infecting a new host?” Often, the methods used to determine this are based on traditional techniques that show whether the agent can replicate in culture or after challenging a small number of experimental animals and looking for signs of disease. In reality, a lack of growth in vitro can simply mean that the conditions provided were unsuitable, and the danger of infection remains. This project will look at the ‘vital signs’ of specific viruses and bacteria to see if they have the potential to be reanimated after experiencing ‘sub-lethal injury’. The student will examine individual viruses and bacteria using fluorescent indicators to determine if membranes are compromised, and molecular biology techniques to determine if genomes are intact. Individual bacteria will be studied for evidence of metabolic activity. The data will be compared to classical but conservative indicators of survival (culturability, cytopathic effect) with the aim of determining the robustness of specific pathogens to environmental challenges such as desiccation, extremely low temperature, and disinfectants. The student will learn and apply quantitative fluorescence microscopy, cryo- electron microscopy, high-pressure freezing and molecular biology techniques, as well as the classical bacteriology and virology skills needed to handle the agents. The work will be conducted in the secure biocontainment laboratory at CSIRO-AAHL, allowing us to investigate highly hazardous agents in a safe and controlled manner. Initial experiments will be conducted with PC1 and PC2 agents. An Honours student would not be required to work with PC3 or PC4 agents but full training will be offered.

Contact supervisor: Dr. Andrew Leis (CSIRO-AAHL): [email protected] 52275435 Suitable for: Honours

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14. Control of early blood and immune cell development: role of Ikaros transcription factors Supervisor/s: Alister Ward Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Members of the Ikaros family of zinc finger transcription factors are important for immune system development, via their effects on key genes involved in this process (John, 2011). Perturbation of these transcription factors can lead to various diseases, particularly lymphomas and leukemias. However, relatively little is known about the most divergent member of this family, Pegasus, which retains a more ancient function compared to the other Ikaros members (John, 2009).

Recent studies in the laboratory have identified reciprocal antagonistic interactions between Pegasus and Ikaros, which may be very important in disease. The aim of this Project is to further investigate the molecular details by expression and purification of recombinant zinc fingers for analysis of DNA binding and protein-protein interaction, and co-expression of Pegasus and Ikaros in cell lines to investigate functional interactions.

This Project will use a range of biochemical and cell biological approaches, including tissue culture, transfection, immunohistochemistry, immunoprecipitation, Western blot analysis, recombinant protein production and various in vitro binding assays.

References: John, L. B., S. Yoong, and A. C. Ward. 2009. Evolution of the Ikaros gene family: implications for the origins of adaptive immunity. J. Immunol. 182:4792-4799. John, L. B. and A. C. Ward. 2011. The Ikaros gene family: transcriptional regulators of hematopoiesis and immunity. Mol. Immunol. 9-10:1272-1278. Contact supervisor: Prof. Alister Ward (Deakin Medical School): [email protected] 52272041

Suitable for: Honours or PhD

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15. Development of miRNA-based early detection technology for emerging infectious diseases Supervisor/s: Chwan Hong Foo, Alister Ward, Andrew Bean Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Emerging infectious diseases, such as Middle Eastern Respiratory Syndrome (MERS), are a significant threat to mankind, especially those with a high mortality rate. Containment of ongoing and future outbreaks, as well as the effective deployment of medical countermeasures, will depend on the development of novel detection technologies that can identify infections early.

This project aims to investigate changes in host biomolecule profiles in response to emerging infectious diseases, like MERS infection, with the goal of developing a novel diagnostic tool. This project utilizes a number of different techniques, ranging from quantitative real time PCR, next-generation sequencing, proteomic assays, and luciferase-reporter assays. Host molecule expression will be studied in a number of animal models, including ferrets. To elucidate the functions of principally important host molecules, various cell and molecular biology approaches will be used.

Contact supervisor: Dr. Chwan Hong Foo (CSIRO-AAHL): [email protected] 0352275380 Suitable for: PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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16. Development of novel anti-viral therapeutics against MERS-CoV Supervisor/s: Celine Deffrasnes, Alister Ward, Andrew Bean Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging virus causing fever, cough, shortness of breath and pneumonia and is associated with 30-50% mortality. Primary infections are thought to occur via contact with infected camels or camel products (milk, meat) and until now, secondary infections have been limited to family members and health care workers in close contact with infected patients. There is no vaccine or therapeutics for MERS-CoV and very little is known about the host-pathogen interactions.

This project aims to investigate host molecules, such as microRNAs, required for/or inhibiting MERS-CoV replication in human cells. This project will use a number of different techniques, ranging from quantitative real time PCR, RNA interference, miRNA mimics/inhibitors, viral inhibition assays, immunofluorescence and high throughput screening. Molecular biology techniques and gene analysis approaches will also be used as well as next-generation sequencing methods.

No direct virus work will be conducted as part of an Honours project but some virus work is possible as part a PhD project.

Contact supervisor: Dr. Celine Deffrasnes (CSIRO-AAHL): [email protected] 0352275758 Suitable for: Honours or PhD This project is subject to final approvals.

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17. Development of therapeutic and diagnostic antibodies Supervisor/s: Daniel Layton, Alister Ward, Andrew Bean Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Highly pathogenic viruses such as avian influenza viruses, MERS and Hendra have acquired the unprecedented and alarming capability to infect humans and pose a continuous risk of fatal animal and human infections. Attempts to avoid or contain outbreaks have been largely unsuccessful and one of the most critical elements to control is rapid diagnosis. It is critical when a new highly pathogenic virus strain emerges globally, that we are able to respond quickly. Part of this response is developing a new diagnostic test. We aim to develop a platform for rapid development of antibodies for diagnosis of emerging infectious diseases and also to use this platform to look for therapeutic antibodies. This project will involve a wide variety of techniques such as protein production and characterisation as well as antibody development, flow cytometry, ELISA and Western blot. This project will also afford the student an excellent opportunity to work in a high bio containment laboratory which is one of very few of its kind world wide. Note: Honours student will not handle PC3 agents. Contact supervisor: Dr. Daniel Layton (CSIRO-AAHL): [email protected] 613 5227 5433 Suitable for: Honours or PhD This project is subject to final approvals.

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18. An investigation of T regulatory cell stability in early life allergic disease Supervisor/s: Peter Vuillermin, Fiona Collier Location: Walter and Eliza Hall and the Geelong Hospital Barwon Health Project description: Thymus-derived natural regulatory T cells (nTreg) programmed by the transcription factor forkhead box P3 (FOXP3) and peripheral-induced regulatory T cells (iTreg) have largely nonoverlapping T-cell receptor repertoires to self-antigens and jointly contribute to immune homeostasis. Several studies have shown that infants with deficits in Treg responses at birth are associated with an increased risk of allergic disease, but the precise nature and underlying basis of these deficits is not known. This project will project will utilise the Barwon Infant Study (BIS) platform to investigate Treg stability among infant who develop food allergy. BIS is an NHMRC funded, population birth cohort study (n = 1069) designed to investigate the early life origins of immune dysregulation in the modern environment. The protocol has included the assembly of a uniquely detailed array of longitudinally assembled environmental data, biosamples and clinical outcomes. The project will involve a combination of cutting edge laboratory work (supervised by Prof Leonard Harrison at the Walter and Eliza Hall Institute) and epidemiology.

Techniques to be used: FACS sorting and in vitro activation of specific Treg populations; intracellular cytokine and expression factor staining; RNA and genomic DNA extraction; determination of gene methylation status; immunoblotting and co-culturing techniques. Immune phenotypes will be related allergic outcomes and a range of putative exposures variables. A high level of statistical support will be provided by the BIS Biostatstics team.

Contact supervisor: Assoc. Prof. Peter Vuillermin (Deakin Medical School): [email protected] 0400071218 Suitable for: PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status. This project is subject to final approvals.

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19. The relationship between nasal colonisation and allergic disease in infants Supervisor/s: Peter Vuillermin, Eugene Athan, Fiona Collier Location: Barwon Health, Geelong Project description: There is mounting interest in the interaction between the human microbiome, immune development and allergic disease. Limited evidence has linked nasal colonisation with pathogenic bacteria during early life with an increased risk of subsequent wheezing illnesses and asthma. This project will utilise the Barwon Infant Study (BIS) platform to investigate the relationship between the early life nasal microbiome and subsequent respiratory health. BIS is an NHMRC funded, population birth cohort study (n = 1069) designed to investigate the early life origins of immune dysregulation in the modern environment. Nasal swabs have been collected at birth, 1, 6 and 12 months of age. Detailed characterisation of the respiratory phenotype, including early life lung function, is under way. The project will involve characterising the nasal microbiome using cutting edge molecular techniques and relating this to respiratory outcomes.

DNA extraction, characterisation of the microbiome using the MiSeq platform, bionformatics and biostatistics. The student will also contribute to BIS fieldwork (involving contact with participating children and families) Statistical support will be provided by the BIS biostatistics team.

Contact supervisor: Assoc. Prof. Peter Vuillermin (Deakin Medical School): [email protected] 0400071218 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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20. A population based investigation of the early life origins of cardiovascular disease Supervisor/s: Peter Vuillermin Location: Barwon Health, Geelong Project description: There is mounting evidence that atherosclerosis, the inflammatory process that underlies cardiovascular disease, begins in early life. Knowledge regarding the factors involved in the initiation and potentiation of atherosclerosis development during early life is of major public health significance. The Barwon Infant Study (BIS) is a population-derived prebirth cohort (n = 1,156) that provides a uniquely detailed array of longitudinal data, biospecimens and physiological measurements.

The proposed PhD program will utilise the BIS platform to conduct an investigation of factors that influence the development of atherosclerosis during the first three postnatal years. The candidate will play a lead role in coordinating and conducting the 3 year BIS reviews. BIS includes a range of cardiovascular outcomes, including ultrasound measurement of carotid and aortic intima media thickness. The PhD will involve a fascinating and challenging mixture of fieldwork, laboratory time and analysis. This program is ideally suited to a clinician candidate with an interest in epidemiology and public health and/or paediatrics, although those with other relevant backgrounds are encouraged to contact the supervisors. Candidates should ideally have first class Honours or equivalent.

Ultrasound techniques will be used to measure intima media thickness of the aorta and carotid arteries. Other measures of cardiovascular health will include blood pressure and pulse wave velocity. The exposures of interest will include infectious illnesses, biochemical markers of inflammation, body composition and growth, diet, activity and lipid profile. A variety of analysis techniques will be used - the candidate will be supported by the BIS laboratory, data management and biostatistics teams.

Contact supervisor: Assoc. Prof. Peter Vuillermin (Deakin Medical School): [email protected] 0400071218 Suitable for: PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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21. Dietary fermentable fibre, short chain fatty acids and allergic disease Supervisor/s: Peter Vuillermin Location: Barwon Health, Geelong Project description: The modern diet is low in plant-derived fermentable carbohydrates (dietary fibre) in comparison to traditional diets. These carbohydrates are the main substrates for the large bowel bacteria, and their fermentation yields short chain fatty acids, which have profound effects on gut epithelial integrity and immune function. There is mounting evidence of an association between the modern, low fibre diet, and allergic disease. The Barwon Infant Study (BIS) is a population-derived prebirth cohort (n = 1,069) that provides a uniquely detailed array of longitudinal data, biospecimens and physiological measurements. This PhD program will utilise the BIS platform to investigate the hypotheses (H1) that high dietary intake of fermentable carbohydrates by the mother during pregnancy and (H2) by the offspring during the first postnatal year are associated with a gut microbiome that produces a specific metabolic pattern of SCFA (esp. elevated levels of butyrate), which in turn, (H3) is associated with reduced risk of allergic disease. This project has the potential to make an importantgrant contribution to international public health policy.

Maternal/infant dietary intake of fermentable carbohydrates will be measured using the Cancer Council Victoria’s Dietary Questionnaire for Epidemiological Studies (DQES) and a modified form of the Phase 3 ISAAC questionnaire. Faecal SCFAs will be measured using a well-established method and expressed as a function of faecal dry matter. The BIS incorporates a range of relevant outcomes including atopic dermatitis and challenge proven food allergy. The candidate will be supported by the BIS laboratory, data management and biostatistics teams.

Contact supervisor: Assoc. Prof. Peter Vuillermin (Deakin Medical School): [email protected] 0400071218 Suitable for: PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status. This project is subject to final approvals.

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22. Genome engineering to control Avian Influenza Virus with RNA interference Supervisor/s: Mark Tizard, John Stambas, Tim Doran Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Avian Influenza Virus still poses a huge threat of devastating global pandemic in the human population, with the major impact in the young adults. The source of this potential global disaster resides in wildfowl. Its amplification through poultry being grown for human food production is what creates the public health threat. This project is based around a major initiative in CSIRO’s Biosecurity Flagship to use precision genome engineering tools to introduce RNA interference constructs to block the ability of the influenza virus to replicate (and thus amplify) in chickens. The team includes a number of scientists and an advanced PhD student. The project will include developing and modifying anti-viral trangene cassette and assessing their biological/anti-viral activity. There are existing cassettes already available to establish these tests against which the improvements can be compared. The student will learn a range of molecular techniques involving use of RNA interference and the assessment of gene expression as well as viral assays. There is significant scope for this work to develop into a PhD project. This project pathway has its ultimate goal in creating a barrier to pandemic Avian Influenza Virus outbreak through optimised precision genome engineering of the chicken.

Contact supervisor: Dr. Mark Tizard (CSIRO-AAHL): [email protected] 03 5227 5753 Suitable for: Honours

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23. Molecular characterization of viral pathogenicity: effect of NDV fusion protein glycosylation Supervisor/s: Grant Peck, Wojtek Michalski, Brian Shiell, Alister Ward Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Newcastle disease virus (NDV) is a paramyxovirus that affects avian species. NDV outbreaks result in high mortality in affected species and have been the source of significant economic loss for the poultry industry. This project aims to better understand the effect of fusion (F) protein glycosylation on NDV pathogenicity by looking specifically at how glycosylation affects F protein cleavage. As an extension to this project (for a PhD degree), a study aimed at understanding the effects of glycosylation on differences in pathogenicity and infectivity of Hendra and Nipah viruses will be undertaken.

Contact supervisor: Dr. Grant Peck (CSIRO-AAHL): [email protected] 03 5227 5793 Suitable for: Honours or PhD

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24. An active genetic factor in milk? Can mother still be controlling baby's immune genes? Supervisor/s: Meagan Gillespie, John Stambas, Mark Tizard Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Breast in best has been the catch-phrase from mid-wives and doctors for decades. It is now known that infants raised on breast milk perform better in a number of developmental measures none more so that immunity. This project will assess the biological activity of a newly identified fraction of milk, known as exosomes, which may enable mothers to have an on-going and direct genetic control of the immune development and immune status of their new-borns.

Mothers provide antibodies passively in colostrum and other aspects of protein composition of milk that are optimised species for species. But the bioactive factors currently known in milk do not, even put together, fully explain the additional benefit of mother’s milk over cow-derived infant formula.

In recent years characterization of the role of microRNAs (small molecule managers of gene expression), which resulted in the award of a Nobel Prize, has been linked to the exosome fraction of milk. Exosomes are found in many biological fluids, particularly serum, and they are known to be potent mediators of microRNA signalling between cells of the immune system. Exosomes and microRNAs are at their most abundant in milk and they are predicted to target genes that are key to the immune system and its development. Working with an established postdoctoral fellow the student will establish a range of molecular genetic assays and biological assays to test the hypothesis that microRNAs in milk are indeed responsible for control of regulation of immune genes. This will help address the fundamental question laid out in the title and could influence future maternal-child management practices and premature neonatal care.

Contact supervisor: Dr. Meagan Gillespie (CSIRO-AAHL): [email protected] 03 5227 5025 Suitable for: Honours

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25. How will urbanisation impact disease emergence? Supervisor/s: Cadhla Firth, Kim Blasdell, Peter Walker, Johnson Mak Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: As a primary driver of environmental change, urbanisation can significantly increase the exposure of human populations to emerging viral diseases. By identifying patterns in the response of viruses to the environmental and ecological changes that occur during urbanisation, we may to be able to understand, predict, and avoid risks from emerging diseases in growing communities. This project will examine viral diversity in a single host species across an environmental gradient ranging from city to pristine environments. There will be an opportunity to contribute to field collections occurring in Northern Australia, as well as to learn state of the art pathogen discovery techniques. This will include next-generation sequencing, viral isolation techniques and standard molecular biology practices, as well as bioinformatics and phylogenetic analysis. This project will add significant insight into the viral response to urbanisation and associated risks of disease emergence in Australian communities and globally.

Contact supervisor: Dr. Cadhla Firth (CSIRO-AAHL): [email protected] 352275639 Suitable for: PhD This project is subject to final approvals.

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26. Engineering the chicken genome to fight food-poisoning bacteria Supervisor/s: Caitlin Cooper, John Stambas, Mark Tizard Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: The fight against the potentially deadly bacteria that cause food-poisoning, Salmonella and Campylobacter, has been waged with antibiotics, public awareness campaigns and legislated food hygiene protocols. As the rise of antibiotic resistance in bacterial pathogens continues we may be left only with hygiene to control these debilitating and sometimes life-threatening infections. However technologies have emerged in the last few years that enable us to engineer animal genomes, to change the way they interact with their own natural microbial communities and with pathogens that may infiltrate them.

This project involves the use of a transposon system and precision genome engineering tools to place antimicrobial proteins in the chicken genome that will enable it to fight these pathogens from within. Working with an international postdoctoral fellow the student will generate and select engineered chicken cell lines to be assessed for expression of the antimicrobial protein and their ability to control adherence and growth of the bacterial pathogens. The elimination, or significant reduction, of these pathogens in the living bird can break the zoonotic pathway for these bacteria to cause disease. Expressing these antimicrobial proteins in the gut tissues specifically will be an important feature of this approach to disease control. The student will also have the opportunity to be involved in the use of retroviral vectors that lead to chicken embryos that have a green fluorescent protein marker throughout their tissues and a red fluorescent protein that should mark the intestinal tissues alone.

The project will provide the student with exposure to the latest technology for genome engineering. It will involve gaining skills in molecular biology, microbiology and designing experimental approaches to assess bioactivity that may ultimately lead to precisely crafted chickens in food production. There is substantial scope to develop this work into a PhD project.

Contact supervisor: Dr. Caitlin Cooper (CSIRO-AAHL): [email protected] 03 5227 5428 Suitable for: Honours

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27. Programming cell death: characterisation of death receptor pathways in bats Supervisor/s: James Wynne, Alister Ward, Michelle Baker Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Emerging infectious diseases pose a significant threat to human and animal welfare. A high proportion of emerging and re-emerging infectious agents are derived from wild-life and in particular bats. Examples such as the henipaviruses (Hendra and Nipah), SARS-like coronavirus and Ebola viruses have all caused significant impact on human and animal welfare. Unlike humans, bats are capably of asymptomatically harbouring and disseminating these highly pathogenic viruses without signs of clinical disease. Recent work within our laboratory has demonstrated that Hendra virus sensitises bat cells to apoptotic cell death, through TNF signalling pathways. Apoptosis, or programmed cell death, is an important anti-viral mechanism in many species. We propose that apoptosis may be a key factor which enables bat cells to maintain asymptomatic viral infection.

“Your mission, if you choose to accept it”: 1) characterise the TNF and apoptosis related genes within the Australian black flying fox, 2) examine the apoptotic response of bat cells to highly pathogenic viruses such as Hendra and Nipah virus, 3) compare the apoptotic response of bat cells with more susceptible species, including human and mouse.

Primarily based at the CSIRO Australian Animal Health Laboratory, you will join a dynamic and successful research group. Little research has been reported on this subject and the student will therefore have the ability to conduct truly novel - and high impact- science. The project will utilise a wide range of technologies and disciplines including molecular biology, genomics, proteomics, microscopy and bioinformatics.

Contact supervisor: Dr. James Wynne (CSIRO-AAHL): [email protected] 0352275602 Suitable for: PhD

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28. Cytokine receptor signaling in bats Supervisor/s: Michelle Baker, Cliff Liongue, Alister Ward Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Bats have been identified as reservoir hosts for a number of zoonotic viruses, including Hendra, SARS, Rabies and Ebola that although lethal in most other mammals, these viruses rarely lead to clinical or pathological consequences for bats. It is possible that the long co-evolution of bats with viruses has led to the development of immune mechanisms for the control of viral replication that are not present in other species. The members of the cytokine signaling pathway are key regulators of immunity and inflammation and play an important role in antiviral immunity. This project will focus on the characterization of cytokine receptors and signaling molecules in bats to determine whether differences in cytokine signaling play a role in the ability of bats to control viral infections. A bioinformatics approach using the whole genome sequence of bats will be used to identify cytokine receptor genes. The sequence information obtained through bioinformatics will be used to design primers to examine transcription of genes in normal bat tissues and virus infected cells by qRT-PCR and functional studies will be used to examine the cytokine signaling pathways. Understanding how bats control viral infections has important implications for developing novel therapeutics for the treatment of similar diseases in humans and other mammals.

Contact supervisor: Dr. Michelle Baker (CSIRO-AAHL): [email protected] 03 5227 5052 Suitable for: Honours or PhD

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29. Mosquito and virus: genomics arms race Supervisor/s: Prasad Paradkar, Jean Bernard Duchemin, Peter Walker, Alister Ward Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Viruses like dengue, chikungunya and West Nile virus, transmitted by mosquitoes, are major causes of infections around the world. These mosquitoes and viruses have evolved over millions of years to coexist. This project will study the co-evolution of the mosquito immune system and immune evasion mechanism of viruses. Using bioinformatics and molecular biology techniques, initial studies will identify the specific amino acid residues in mosquito immune proteins that are targeted by viral proteins to overcome the immune response. The validation of these in vitro studies will be performed using mosquito infections.

The project will reveal the evolutionary arms race between viruses and mosquitoes and will help in determining the genetic basis of vector competence.

Contact supervisor: Dr. Prasad Paradkar (CSIRO-AAHL): [email protected] 0352275462 Suitable for: PhD

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30. Is the pigeon crop the avian mammary gland? Supervisor/s: Tamsyn Crowley, Anthony Keyburn, Meagan Gillespie Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Avian mammary gland? Birds don’t lactate, or do they? Over the last few years we have been investigating an intriguing biological phenomenon present in a select group of birds, namely the production of crop milk in pigeons. Crop milk, also known as ‘pigeon milk’, is a nutrient substance produced by both male and female pigeons to feed their young. As with mammalian milk, crop milk is essential for squab growth, providing both nutritional and immune benefits. During the process of pigeon ‘lactation’, a curd-like substance is regurgitated from the crop to the squab. Crop milk is predominately made up of protein and fat with a small amount of carbohydrate. High levels of morbidity or mortality was observed when pigeon squabs were fed with artificial crop milk suggesting there is a unique factor or factors present in pigeon milk required for squab growth and development. It has been shown that pigeon milk contains IgA antibodies, providing further evidence to suggest that it is more than just a nutrient based substance. Conversely, in a 1952 study where pigeon milk was fed to chickens, their rate of growth improved by 38%. We have since replicated this study and found that the GI tract of chickens fed pigeon milk were colonized with Veillonella, a pre-biotic bacteria found in pigeon milk, that has also been shown in humans to be shared between the maternal and neonatal gut ecosystem via breastfeeding. Our group has also begun investigating the main proteins in pigeon milk, with a particular interest in the evolution of these proteins. We are interested to see if there is any cross over with proteins in the milk of both platypus and echidna, since this special group of marsupials both lay eggs and suckle their young. To date we have gained a great deal of knowledge and insight into this magnificent biological phenomenon and we will continue to explore if the pigeon crop is indeed the avian mammary gland.

Contact supervisor: Dr. Tamsyn Crowley (Deakin Medical School): [email protected] 61352271328 Suitable for: Honours or PhD

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31. Understanding the role of NOX2 in influenza-induced hypercytokinemia in a knockout chicken cell line

Supervisor/s: Siying Ye, John Stambas Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Infection with highly pathogenic avian influenza (HPAI) A virus usually causes dysregulation of cytokine production (“cytokine storm”) that leads to multiple organ failure or death. The role of reactive oxygen species (ROS) and the contribution of NOX2, the catalytic subunit of the phagocyte NADPH oxidase, was shown to contribute to pathogenesis of avian influenza virus. In order to study the mechanism of avian influenza virus pathogenesis and the role of ROS in the natural host, i.e. chicken, the overarching aim is to generate the world’s first knockout chicken (NOX2-/-) using cutting-edge genome editing technology, CRISPR (clustered regularly interspaced short palindromic repeats)/CRISP-associated protein (Cas)). A proof-of-concept study will be first performed in HD-11 chicken macrophage cell line to examine gene-knockout efficiency and the associated immunologic consequences following influenza A virus infection to lay the foundation for the generation of NOX2-/- chickens in the future. NOX2 will also be knocked-down in HD-11 cells using traditional gene silencing technique by transfecting cells with siNOX2. This will be used as a NOX2-knockdown infection model.

The techniques to be used in this project include PCR, quantitative real-time PCR for measurement of gene expression, cloning, cell culture, transfection or genetic manipulation of cells, RNA extraction and purification, gel electrophoresis of nucleic acids, influenza A virus propagation and infection.

Contact supervisor: Dr. Siying Ye (Deakin Medical School): [email protected] 03 5227 5766 Suitable for: Honours

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32. The development of host-derived antivirals for emerging infectious disease threats Supervisor/s: Cameron Stewart, Andrew Bean, Daniel Layton, John Stambas Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Zoonotic viruses emerging from wildlife and domesticated animals pose a serious threat to human and animal health and are recognised as the most likely source of the next pandemic. Containment of emerging infectious disease (EID) outbreaks is often difficult due to their unpredictability and the absence of effective control measures, such as antiviral therapeutics for humans.

The innate immune system is the body’s first, and in many instances, most important defence mechanism against invading pathogens. A competent innate immune response helps protect the host from many deadly viral pathogens, with interferon (IFN) representing a key front line defender with broad-spectrum antiviral activity. With this in mind, many viruses attempt to counteract this host response by blocking the production of IFN, adding to their pathogenicity.

To identify new strategies to combat EIDs, we recently performed a genome-wide analysis of the pathways within a human cell associated with Hendra virus infection. Hendra virus, like all viruses, is an obligate pathogen - it cannot replicate without commandeering or “hi-jacking” host cell machinery. We have discovered that Hendra virus infection is reliant on poorly-characterised host proteins. Preliminary work shows that several host proteins required for Hendra virus infection are potent modulators of IFN signalling and downstream IFN activity.

We are offering both Honours and PhD projects to characterise host proteins associated with virus replication and disease. The project will develop the student’s expertise in protein biochemistry, molecular biology, virology and immunology. Our research team, working in the advanced biocontainment settings of AAHL, gives us a global competitive advantage to study host-virus interactions.

Contact supervisor: Dr. Cameron Stewart (CSIRO-AAHL): [email protected] 03 5227 5601 Suitable for: PhD

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33. Role of Zinc-alpha-2-glycoprotein (ZAG): Relationship between Disease and ZAG Glycosylation Supervisor/s: Wojtek Michalski, Grant Peck, James Wynne, Tamsyn Crowley, Alister Ward Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Zinc alpha 2-glycoprotein (ZAG) is a protein of interest because it has been implicated in several important functions in the human body. Despite this, the functional role(s) of ZAG remains to be fully elucidated. The structure of ZAG is similar to the MHC class I antigen-presenting molecule; hence, ZAG may have a role in the immune response. ZAG is detectable in many tissues, including milk. The project will explore the relationship between ZAG expression in human milk, its glycosylation status and disease. Although designed as an Honours project it is likely to be developed into a PhD project. Contact supervisor: Dr. Wojtek Michalski (CSIRO-AAHL): [email protected] 03 5227 5772 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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34. Dissecting the viral entry using super-resolution microscopy and electron microscopy Supervisor/s: Johnson Mak, Sean Pham, Megan Garvey Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: Current dogma asserts that HIV-1 particles have static structures, in which the cone-shaped virion core is released into target cells uponmembrane fusion. Using a combination of scanning EM, cryo-EM tomography and super-resolution fluorescence microscopy, we have obtained direct evidence to refute the current dogma that virions are largely ‘static’ during viral entry. We have observed that HIV-1 undergoes significant structural changes upon receptor engagement (but prior to virus entry), which challenges a long held believe in the field of virology. This project will further investigate HIV-1 entry process as well as examining whether this unexpected observation is a general phenomenon for other viruses, such as Hendra Viruses, SARS coronaviruses and Vaccinia Viruses. Un-tagged or tagged viruses will be use to infect target cells under tissue culture infection conditions. The infection process will be followed via both fluorescent imaging and electron microscopy. Molecular biology based genetic / protein engineering are used on a regular basis to discern the mechanism of various biological process. Virus production and purification via ultracentrifugation through molecular biology techniques are done routinely. Virological assays are employed frequently to validate our various experimental approaches appropriate reflect the biological processes that are being investigated. Imaging techniques (including immunofluorescence, super-resolution microscopy, thin-section electron microscopy, immune-gold EM, cryo EM, tomography, and single particle analysis) are either done in house or in collaboration with researchers within Australia to determine the biological processes / mechanism that are involved in HIV entry or release. Honours student will only work with PC2 materials.

Contact supervisor: Prof. Johnson Mak (Deakin Medical School): [email protected] 04 3956 2574 Suitable for: Honours or PhD

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35. Assembly and maturation of human immunodeficiency virus type 1 Supervisor/s: Johnson Mak, Keith Khoo, Bill McKinistry Location: CSIRO, CMSE Parkville Project description: The assembly and maturation of HIV-1 is driven by oligomerization and the proteolytic processing of HIV-1 Gag precursor proteins. One of the major obstacles to study HIV-1 assembly and maturation biochemically is the lack of the large quantity of full-length purified HIV-1 Gag proteins for analyses. Our lab has overcome this challenge by establishing novel procedure to generate significant amount of HIV-1 Gag recombinant protein for investigation. The research project is based on biophysical analysis of HIV-1 proteins that are generated through recombinant protein production system. Un-tagged or tagged recombinant proteins will be generated through in vitro protein expression systems, and chromatography techniques (such as FPLC) will be used for protein isolation and purification. Molecular biology based genetic / protein engineering approaches are used on a regular basis to discern the mechanism of biological process. Surface Plasmon resonance and isothermal titration calorimetry will be used to evaluate the biophysical property of HIV-1 Gag proteins during viral assembly and maturation. Desirable protein conditions will also be defined for the generation of mono-dispersed population of viral oligomeric proteins or protein complexes for crystallization trials and structural determination. Imaging techniques (such as thin-section electron microscopy, immune-gold EM, cryo EM, tomography, and single particle analysis) are also done in conjunction with other lab members for structural determination of the protein complex. Honours student will only work with PC2 materials.

Contact supervisor: Prof. Johnson Mak (Deakin Medical School): [email protected] 04 3956 2574 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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36. How does human immunodeficiency viruses type 1 diversify? Supervisor/s: Johnson Mak, Caryll Waugh, Sahar Eid Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: The resurgence of HIV-1 in two previously ‘cured’ Boston-patients in 2014 highlights the ability of HIV-1 to propagate in vivo is distinct from many assumptions that we have made from in vitro studies. Amongst various traits of HIV-1, the diversity of HIV-1 in vivo is significantly associated with the health status of the patients. Within six years of viral infection, a single founder HIV-1 evolves to produce HIV-1 quasispecies in a single patient that is greater than the annual global diversity of influenza A virus. This rapid increase in viral heterogeneity contributes to immune escape that leads to the eventual loss of the immune control and the development of AIDS. The divergence of viral sequences is mediated by the infidelity of viral Reverse Transcriptase (RT) to introduce mutations and the capacity of retroviral recombination to shuffle genetics materials between genomes. In contrast to previous studies that used non-viral reporter systems to estimate HIV-1 mutation and recombination rate, we have directly measured the HIV-1 recombination and mutation rates in T-lymphocytes to be 1.5 x10^-3 and 4.6 x10^-5, respectively, using next generation sequencing. Tissue culture based infection system and molecular biological tools are the foundation of this research work. Primary cells are isolated from health donors. Identical twin blood donors are also used to discern the potential genetic contributions to virus evolution. State of the art molecular biological tools and virological techniques (including siRNA knockdown in primary cells, virus production and purification via ultracentrifugation, FACS, immune-based detection system, antiviral drug testing and mass spectrometry) are either done in house or in collaboration with researchers within Australia to dissect the process of HIV replication. Genetic modified viruses are also being using to infect primate animal models to evaluate the virus evolution process in vivo. Honours student will only work with PC2 agents

Contact supervisor: Prof. Johnson Mak (Deakin Medical School): [email protected] 04 3956 2574 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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37. Device and biofilm infections Supervisor/s: Eugene Athan, Melanie Thomson, Richard Page Location: School of Medicine, Deakin University, Waurn Ponds Campus Barwon Health Project description: Orthopedic infections, in particular prosthetic joint infections are complex and costly to health services. Patients experience significant morbidity, loss of quality of life and prolonged length of stay in hospital. The optimal management requires a multidisciplinary model of care between Orthopaedic surgeons and Infectious Diseases specialists, with nursing and allied health support. Infections of bones and joints in particular prosthetic joints remain a major medical and surgical challenge. This is further complicated by the emergence of multiresistant bacterial infections such as MRSA, VRE and extended spectrum betalactamase producing Gram negative organisms.

We propose detailed clinical, epidemiological and microbiological analyses of all cases of orthopedic infections including biofilm studies in vitro and an in vivo mouse model.

The project will involve: • Analyses of cases with orthopedic infections • Microbiological analyses of isolates causing infections including biofilm studies • Development of in vivo mouse model of prosthetic infection Contact supervisor: Assoc. Prof. Eugene Athan (Barwon Health): [email protected] 42152375 Suitable for: Honours or PhD This project is subject to final approvals.

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38. Mycobacteria ulcerans flesh eating bacteria Supervisor/s: Daniel O'Brien, Eugene Athan, Melanie Thomson, James Wynne, Julie Pasco Location: Barwon Health, Geelong Project description: Mycobacterium ulcerans (MU) is an emerging infectious disease that is endemic in coastal regions of Victoria. Commonly known as the Bairnsdale ulcer or ‘flesh-eating disease’. Number of reported cases in Australia is increasing and new endemic areas are being recognized. Worldwide it is the third most common mycobacterial disease after tuberculosis and leprosy with the greatest disease burden found in rural and remote regions of west and central Africa.

MU causes destructive lesions of the skin and subcutaneous tissue that leads to severe ulcers affecting mainly upper and lower limbs, but can affect any part of the body. This can often result in reconstructive surgery, hospitalization, long-term morbidity and significant cost. Since the outbreak in the Bellarine Peninsula began in 1998, more than 275 patients with MU acquired on the Bellarine Peninsula have been managed by clinicians of Barwon Health and local general practitioners in the region. The incidence of MU disease in the region continues to increase, with a higher proportion of young children affected.

The disease is a significant health issue for the communities of the Bellarine Peninsula and Geelong region. The environmental reservoir and mode of transmission for the disease remain unknown. However it is known that the organism lives in the environment, especially associated with soil and water. MU disease also affects wildlife including possums and koalas, and domesticated animals such as dogs, horses, cats and alpacas. Insect vectors such as mosquitoes and flies have been proposed to have a role in the transmission of the disease. A “One Health” collaborative approach has been undertaken in studying MU disease.

The project will involve: • Epidemiological and clinical analysis of large patient cohort • Microbiological laboratory analyses of isolates and therapy • Genotyping of strains • Serosurvey of human population Contact supervisor: Assoc. Prof. Daniel O'Brien (Barwon Health): [email protected] 42152375 Suitable for: Honours or PhD

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39. Infective endocarditis in the 21st century Supervisor/s: Eugene Athan, Melanie Thomson, Julie Pasco Location: Barwon Health, Geelong Project description: Infective endocarditis (IE) is a complex multisystem disease with a mortality of up to thirty percent. Despite major advances in medical care this overall mortality rate has not improved. The epidemiologic and clinical features of infective endocarditis in the twenty first century have changed dramatically. Historically during the twentieth century infective endocarditis was a disease affecting younger patients with underlying rheumatic heart disease and was mainly caused by oral Streptococci and resulting in classical sub-acute presentations.

The contemporary picture of infective endocarditis commonly affects elderly patients with extensive health care contact, often involving prosthetic valves, cardiac devices and is caused by Staphylococci, in particular, Staphylococcus aureus predominates. Increasingly other organisms such as Enterococci and Candida fungal infections are being reported. Despite increased age and co-morbidities surgical treatment such as valve replacement and cardiac device removal is performed increasingly in over half of all cases. Parenteral antibiotic therapy is increasingly being delivered safely at home in stable and carefully selected patients. Novel antifungal agents such as Caspofungin, have improved the outcome for patients deemed unsuitable for surgical intervention.

Infective endocarditis in the 21st century continues to be an important cause of morbidity and mortality. It has increasingly become a disease associated with modern health care interventions. We would like to better understand the microbiological and epidemiological features of all cases of infective endocarditis. Laboratory typing of isolates will also be performed.

This project will involve: • Collection of microbiological isolates • Analyses of all cases of IE risk factors and patient outcomes • Epidemiologic studies icluding surveys and interventional population studies.

Contact supervisor: Assoc. Prof. Eugene Athan (Barwon Health): [email protected] 42152375 Suitable for: Honours or PhD

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40. Dissecting how rhoptry proteins help malaria parasites secure their survival in host red blood cells

Supervisor/s: Tania de Koning-Ward, Natalie Counihan Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Malaria is one of the most significant infectious diseases worldwide and is caused by infection with Plasmodium species. Malaria parasites must invade and remodel its host cell to survive and to achieve this, they sequentially secrete novel proteins from a set of specialized organelles into the host cell. One of these specialised organelles is termed the rhoptry. Proteins lcoalised to the bulb region of this structure are not only unique to malaria parasites but they also essential for parasite survival.

The aim of this project is to investigate how rhoptry bulb proteins gain access to the host red blood cell and if these proteins remodel the host red blood cell in a manner that makes it hospitable for Plasmodium growth and survival. To address these aims, a series of transgenic parasites will be created by reverse genetics that enables the trafficking and localization of several rhoptry proteins to be followed across the cell cycle. Additionally, the consequence of ablating expression of rhoptry proteins on parasite growth and survival will be investigated.

For this project a diverse range of techniques will be utilized. These include molecular (PCR, cloning, sequencing), protein (expression, purification, western blotting) and cell biological techniques (growth assays, immunofluorescence analysis, live cell and high resolution imaging). Findings from this project will provide a better understanding of how malaria parasites secure their own survival within their host, leading to the development of effective and novel therapeutics.

Contact supervisor: Assoc. Prof. Tania de Koning-Ward (Deakin Medical School): [email protected] 52272923 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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41. Targeting the Achilles’ heel of the malaria parasite Supervisor/s: Tania de Koning-Ward Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: The Plasmodium parasites that cause malaria are one of the most successful pathogens to infect mankind. By exporting hundreds of their proteins into red blood cells, Plasmodium parasites are able to drastically modify their host cell, enabling them to replicate and cause disease while avoiding destruction by the human host. In one of the biggest breakthroughs in malaria research of recent times, we have revealed that malaria parasites have an Achilles’ heel: they rely on the use of single protein export machinery (termed PTEX) to provide a gateway for all these parasite proteins to enter red blood cells. Thus targeting PTEX provides a powerful mechanism to block hundreds of proteins involved in parasite virulence and survival from accessing the host red blood cell.

This project aims to unravel how PTEX components are assembled at the interface between the parasite and host cell so that protein export can occur. Secondly, by trapping PTEX in the process of exporting proteins, this project aims to identify novel components of PTEX that are required for trafficking the diverse types of cargo that must enter the host red blood cell to facilitate parasite survival. The information gained from this project will help identify novel strategies to block PTEX function and hence kill this deadly pathogen. The project provides the applicant with a very broad skills base including molecular biology techniques (eg. PCR, cloning, sequencing, southern blotting and reverse genetics), cell culture (eg. parasite culturing, transfection), protein techniques (Western blotting, immunoprecipitation) and cell biology techniques (immunofluorescence assays, live cell imaging using super resolution microscopy).

Contact supervisor: Assoc. Prof. Tania de Koning-Ward (Deakin Medical School): [email protected] 52272923 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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Mental Health & Neuroscience

42. The relationship between maternal stress during pregnancy and offspring behaviour and mental health

Supervisor/s: Peter Vuillermin, Peter Vuillermin Location: Barwon Health, Geelong Project description: The proposed PhD program will utilise the Barwon Infant Study (BIS) platform to investigate the relationship between maternal antenatal stress and offspring neurodevelopment. The BIS protocol includes validated measures of maternal stress and mental health during pregnancy and the first years of the child’s life. The candidate would be involved in administering the 2 year BIS review, which would include developing expertise in a number of validated measures of childhood socio-emotional development (such as the Bailey’s Developmental Inventory and Achenbach Child Behaviour Checklist). The project is well suited to a psychology graduate with an interest in working with children. There are a number of ways in which the BIS biosamples could be used to enhance this project. For example, there is a planned investigation of the relationship between maternal antenatal stress and the offspring’s epigenetic profile. There is also substantial opportunity to develop the synergies between the proposed study and other aspects of BIS.

Maternal stress and mental health are measured repeatedly during pregnancy and the first years of the child’s life using the Perceived Stress Scale and the Edinburgh Postnatal Depression Scale. The child’s socio-emotional development is primarily measured at 2 years of age using the Bailey’s Development Inventory and the Achenbach Child Behaviour Checklist. A wide range of covariates have been captured. Synergistic work regarding the antenatal factors and the infant’s epigenetic profile are under way. A variety of analysis techniques will be used – the candidate will be supported by the BIS data management and biostatistics team.

Contact supervisor: Assoc. Prof. Peter Vuillermin (Deakin Medical School): [email protected] 0400 071 218 Suitable for: Honours This project is subject to final approvals.

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43. Clinical factors involved in the effects of N-acetyl cysteine treatment in depression Supervisor/s: Olivia Dean, Michael Berk Location: Barwon Health, Geelong Project description: Depression is a common mental illness that is plagued by treatments restoring only partial functionality to individuals. The need for novel treatments is high and with the advancements in the understanding of the biology of depression, there is an abundant opportunity to develop new therapies. Our team has taken a biological approach to the treatment of depression, trialling N-acetyl cysteine as an adjunctive treatment for both major depression and bipolar disorder. N-acetyl cysteine in an anti-inflammatory and has antioxidant properties. Additionally, N-acetyl cysteine (traditionally used as an antedote to paracetamol overdose) modulates glutamate and enhances neurogenesis. These are all factors beleived to be involved in both unipolar and bipolar depression. The current project involves data exploration of the datasets from two randomised, controlled trials of N-acetyl cystein for depression. The student would be invovled in exploring factors that predict treatment response to N-acetyl cysteine. Given the richness of these databases, there is opportunity to explore symptoms, functionality, quality of life and demographic factors invovled in bipolar and unipolar depression.

Contact supervisor: Dr. Olivia Dean (Deakin Medical School): [email protected] 42153300 Suitable for: Honours

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44. Clinical factors involved in the effects of N-acetyl cysteine treatment in autism Supervisor/s: Olivia Dean, Michael Berk Location: Barwon Health, Geelong Project description: Autism is a disorder that currently has limited treatment options. Most therapies are focused on addressing behavioural issues, rather than target core biological factors that may be contributing to the development of autism. Our team has conducted a randomised, controlled trial of 109 children with autism. The study is based on the current understanding of the underlying biology of autism and involved treatment with N-acetyl cysteine. Research suggests that oxidative stress and inflammation may be important factors that contribute to autism. N-acetyl cysteine is an amino acid with both anti-inflammatory and antioxidant properties. This trial involved 6 months of N-acetyl cysteine treatment, compared with placebo, in addition to any usual treatment. The current project involves data exploration of factors that may predict outcomes of treatment. The student would be required to employ statistical techniques to explore the dataset. The results of these data exploration are likely to result in pubilcation of the findings, given the highly novel and biological nature of the trial.


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45. Novel therapies for Huntington’s disease: targeting nervous system and metabolic dysfunction Supervisor/s: Laura Gray, Sean McGee Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Huntington’s disease is a devastating genetic disorder which causes striking neurological symptoms of motor dysfunction, cognitive impairment and mood dysregulation. Less well recognised but equally contributing to the decline of function and quality of life are the peripheral changes in metabolic function, insulin and glucose regulation, and muscle and fat distribution. The common factor which links the neurological and peripheral symptoms is disturbance in the intracellular pathways which respond to cell stress, including the processes regulating oxidative stress.

Our recent studies have highlighted a novel drug therapy which modulates oxidative stress and has shown great promise in treating the motor dysfunction associated with this disease. We will therefore investigate the potential of using this novel therapy to address both the peripheral metabolic and central neurological symptoms of Huntington’s disease. This project will involve administration of the novel drug to a genetic mouse model of Huntington’s disease.

The student involved in this project would develop skills in animal behavioural testing, metabolic profiling, molecular biology, protein marker analysis and data analysis. The student would be encouraged to develop their knowledge of both metabolic disorders and neurobiology, and would be encouraged to develop their independence in the laboratory with the support and guidance from engaged and enthusiastic supervisors. This project represents an opportunity to be involved in a novel and innovative study with strong prospects for high-impact publication and direct benefits for patient health.

Contact supervisor: Dr. Laura Gray (Deakin Medical School): [email protected] 52272852 Suitable for: Honours or PhD This project is subject to final approvals.

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46. Reintroducing good old friend: insulin like growth factor-1 protection against neuronal insults Supervisor/s: Jagat Kanwar, Bhasker Sriramoju, Rupinder Kanwar Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Neurological diseases are typically being characterised by various insults that culminate with a significant loss of the neurons. The result is the permanent brain where the damaged neurons can neither be replaced nor can the existing neurons compensate the loss as they have a limited proliferating capacity. On the other hand, delivery of the therapeutics to the brain is quiet challenging due to the prevailing blood brain barrier (BBB) that is highly selective in regulating the traffic in and out of the brain. Combining the complex nature of the BBB and the limited neuronal proliferation, treatment aiming for brain disorder therapy is always challenging but certainly rewarding. It has been reported that insulin like growth factor-1 (IGF-1) is represented as a pleiotropic polypeptide with multifunctional activities and has a strong protective potential in both the central and peripheral nervous systems. Hence, studying its application against a variety of neuronal insults can be fruitful and being an endogenous growth factor toxicity issues are even nullified. The current project aims to study the protective actions of insulin like growth factor-1 against a variety of toxic insults towards the neurons and at a later stage the in vitro results will be escalated to in vivo studies. The novelty of the project is it involves the encapsulation of IGF-1 in biodegradable nanoparticles that are surface modified with the brain specific marker for effective delivery and to minimise the non-specific biodistribution. To conclude, IGF-1 is anticipated to show a positive outcome against the neuronal insults considering its endogenous activity.

Contact supervisor: Prof. Jagat Kanwar (Deakin Medical School): [email protected] 52271148 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status. This project is subject to final approvals.

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47. Later life mood, anxiety and personality disorders and treatment Supervisor/s: Lana Williams, Julie Pasco, Sharon Brennan, Kara Holloway Location: Barwon Health, Geelong Project description: The aim of this project is to investigate later life mood, anxiety and personality disorders, their treatment and co-morbidities in men and women participating in the Geelong Osteoporosis Study. Mood, anxiety and personality disorders will be assessed utilising the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition (SCID I & II/NP) and psychological symptomatology using the Hospital Anxiety and Depression Scale (HADS). Information on demographic, lifestyle, medication use and somatic illness is obtained via questionnaire.

The project will utilise epidemiological study methods; regression techniques will be used to determine associations between psychological disorders and symptoms and various health outcomes. This project will be undertaken within the Psychiatric Epidemiology branch of the Epi-Centre for Healthy Ageing, located in the IMPACT SRC (Innovations in Mental and Physical Health and Clinical Trials).

Contact supervisor: Dr. Lana Williams (Deakin Medical School): [email protected] 61 3 4215 3303 Suitable for: Honours or PhD

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48. Stressed, sick and sad; interactions between inflammation and mood. Supervisor/s: Laura Gray Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Up to 20% of the population will experience a period of clinically identified depression over their lifetime, and many people struggle with this illness throughout their lives. However despite the prevalence of this disorder we do not have a good understanding of how the many risk factors for depression interact to influence mood. Substantial evidence suggests that dysregulation of the immune system and inflammation are strongly associated with mood disorders, although it is unclear how peripheral inflammation affects the brain. This project will involve administration of a stimulant of the immune system to mice, over both the short and long term (days vs weeks). We will examine the resulting changes in inflammatory markers, in the periphery and the brain, and assess how immune cells, neurons and glial cells change their function and activity in response to inflammation. We will also examine changes in behaviour and cognition in mice in response to inflammation. Changes in stress hormones will also be measured, and correlated with any changes in measures of immune function. This project represents a unique opportunity to learn about the interfaces between immunology, endocrinology and neuropsychiatry. This is an exciting area which is at the cutting edge of current research.

Students will develop skills in cell culture, animal handling and injections, ELISA, flow cytometry, HPLC and behavioural testing. Students will be encouraged to extend their theoretical and practical knowledge in a range of areas, and to develop independent but guided research.

Contact supervisor: Dr. Laura Gray (Deakin Medical School): [email protected] 52272852 Suitable for: Honours This project is subject to final approvals.

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49. Qualitative analysis of the effects of N-acetyl cysteine treatment in unipolar depression Supervisor/s: Olivia Dean, Linda Byrne Location: Barwon Health, Geelong Project description: Very few clinical trials incorporate a qualitative component into their design. This novel project will involve the analysis of qualitative data collected as part of a study investigating the effects of N-acetyl cysteine, a natural therapy added on to participant’s usual treatment for unipolar (clinical) depression. The clinical trial has been completed and the quantitative results have been published. However, as part of this study, case notes have also been recorded detailing participant’s subjective feelings of changes in their symptoms while on the trial. Similarly, notes have also been collected on subjective clinician opinions on how the participant’s symptoms have changed over the course of the trial. The project will involve the qualitative analysis of clinical trial case notes of 273 participant files that have been entered into the database. This project would involve the collation and analysis of these qualitative notes to determine themes surrounding the potential benefit of the N-acetyl cysteine treatment.


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50. Evaluating the relationship between anxiety symptoms and dietary intake those with depression

Supervisor/s: Felice Jacka, Adrienne O'Neil Location: Barwon Health, Geelong Project description: We are conducting a Randomised Controlled Trial (RCT) to investigate the efficacy of dietary improvement as a treatment strategy for Major Depressive Disorder. This trial is based in Melbourne; however, the project can be co-based in Geelong. This project will investigate the relationship between anxiety symptoms and dietary intake in this clinically depressed population. We are interested to know whether dietary intakes and overall quality are correlated with the level of comorbid anxiety symptoms experienced by people with major depression. Dietary intakes and quality will be measured using a validated FFQ and algorithm, as well as gold-standard food diaries. Data will be drawn from the baseline questionnaires completed by trial participants. As well as supervision from senior academic staff, students will receive support from qualified dietitians in this undertaking. They will gain valuable hands-on experience of research in the context of a randomised controlled trial. This project would ideally suit those with a psychology background.

Contact supervisor: Assoc. Prof. Felice Jacka (Deakin Medical School): [email protected] 4215 3302 Suitable for: Honours

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51. Validation of a brief diet quality screening tool Supervisor/s: Felice Jacka, Adrienne O'Neil Location: North Yarra Community Centre, Collingwood, Melbourne Project description: We are conducting a Randomised Controlled Trial (RCT) to investigate the efficacy of dietary improvement as a treatment strategy for Major Depressive Disorder. This trial is based in Melbourne; however, the project can be co-based in Geelong. This project will investigate the utility of a brief dietary screening tool as a means of determining diet quality in people with major depression. To date, there are few available brief questionnaires to ascertain overall diet quality. Data will be drawn from the baseline questionnaires completed by RCT participants. Results will be compared to validated food frequency questionnaires and seven day food diaries. As well as supervision from senior academic staff, students will receive support from qualified dietitians in this undertaking. They will gain expertise in the development and evaluation of questionnaires, as well as experience of real world research in the context of a randomised controlled trial. This project would suit those with either a nutrition background or a psychology background.


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Development & Cancer

52. The role of C-type natriuretic peptide in ovary and placenta Supervisor/s: Bryony McNeill Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: C-type natriuretic peptide (CNP) is a signalling molecule which plays an important role in growth and development. Particularly high levels of expression of this peptide have been identified in the placenta and ovaries. Although the precise role of CNP in these tissues has not been elucidated, recent evidence indicates that it is likely to be an important regulator of oocyte and follicular development, and a possible marker of fetal-maternal wellbeing during pregnancy.

The purpose of this study is to further our understanding of CNP signalling in the normal and diseased ovary and/or placenta. Techniques will include mRNA and protein localisation, hormone assays and molecular biology.

Contact supervisor: Dr. Bryony McNeill (Deakin Medical School): [email protected] 52272294 Suitable for: Honours This project is subject to final approvals.

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53. Role of cytokine receptor signaling in development and disease Supervisor/s: Alister Ward, Clifford Liongue Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: The correct development and maintenance of multi-cellular organisms is supported by systems enabling cells to communicate to one another in response to distinct cues. Cytokines are polypeptides that are produced and secreted by cells following a variety of stimuli, and induce a range of cellular effects via specific cytokine receptors located on the cell surface. These receptors signal to the nucleus via the so-called ‘Jak-Stat-Socs’ signaling pathway to mediate effects on gene transcription and cell physiology that are particularly important in blood and immune cell development (O’Sullivan et al., 2007). Perturbation of this pathway is associated with several diseases, including inflammation and cancer (Lewis et al., 2006; Ma et al., 2007).

This Project aims to further our understanding of the developmental roles of the Cytokine receptor-Jak-Stat-Socs pathway at the molecular level, as well as elucidating how changes in this pathway lead to disease. This approach will provide insight into the underlying biology as well as establishing a platform for the development of therapeutics to combat relevant diseases.

This Project will use zebrafish and other cell model systems to investigate the role of one or more components of the Cytokine receptor-Jak-Stat-Socs pathway by expression studies, as well as gene knockdown and subsequent phenotypic and biochemical analyses.

References; Lewis, R. S., S. E. M. Stephenson, and A. C. Ward. 2006. Constitutive-activation of zebrafish Stat5 expands hematopoietic cell populations in vivo. Exp. Hematol. 34: 179-187. O'Sullivan, L. A., R. S. Lewis, C. Liongue, S. E. M. Stephenson, and A. C. Ward. 2007. Cytokine receptor signalling through the Jak-Stat-Socs pathway in disease. Mol. Immunol. 44:2497-2506. Ma, A. C., A. C. Ward, R. Liang, and A. Y. H. Leung. 2007. The role of jak2a in zebrafish hematopoiesis. Blood 110:1824-1830.

Contact supervisor: Prof. Alister Ward (Deakin Medical School): [email protected] 52272041 Suitable for: Honours or PhD

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54. Generation of induced pluripotent stem cells Supervisor/s: Luis Malaver-Ortega, Alister Ward, Andrew Bean Location: CSIRO (Australian Animal Health Laboratory), Geelong Project description: By modulation of a reduce number of key genes it is possible to modify cellular behaviour. By this mean, Induced pluripotent stem cells (iPSCs) have been generated. iPSCs possess the pluripotent characteristics of Embryonic Stem cells (ESC) with the advantage of being generated from cells from virtually any tissue. iPSCs can also differentiate in vitro and in vivo into a wide range of cell types including Primordial Germ Cells (PGCs), the earliest progenitor that gives rise to the gametes in animals. This makes them excellent candidates for gene manipulation. This project aims to generate iPSCs cell lines and characterize their differentiation potential using state-of-the-art technology in cell and molecular biology and immunological techniques developed in the laboratory.

A wide range of techniques will be utilized for this project including: cloning PCR, viral transfection, recombinant DNA, immunostaining, germ cell characterization and transplantation, quantitative real time PCR, luciferase-reporter assays, histological techniques, cytometry, cell culture of pluripotent stem cells and germ cells and in vitro differentiation of pluripotent cells.

Contact supervisor: Dr. Luis Malaver-Ortega (CSIRO-AAHL): [email protected] 610352275243 Suitable for: Honours or PhD This project is subject to final approvals.

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55. Translational research of tailored neoadjuvant chemotherapy for newly diagnosed breast cancer

Supervisor/s: Mustafa Khasraw, Andrea Muscat, Jason Hodge, David Ashley Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: We are conducting a study in the neoadjuvant setting (chemotherapy prior to surgery) in newly diagnosed breast cancer. In addition to assessing the effectiveness of the treatment, a small portion of the tumour will be used to test new treatment options. Fresh samples, will be taken prior to commencement of treatment will be used to create a cancer biology model. This model is an effective method to assess how breast cancers respond to new drug treatments. There will be two points where tumor samples obtained for the diagnosis of breast cancer may have available tissue. The first one is when the tumor is diagnosed by a biopsy. The second one when any remaining tumor is removed at operation following the chemotherapy treatment. Sample taken during the initial diagnosis procedure will allow us to create a cancer cell model. We will also use a small portion of the surgical sample to create a second cancer cell model, compare the samples and use this to determine if the remaining cells respond to other treatments following initial chemotherapy. Further work will be done using the tumor models in the laboratory that aims to discover why the tumor initiating cells or the so called “cancer stem cell” can stay dormant (quiet) without dividing for some time and then change behavior and start dividing again, multiplying and growing to larger tumour and spread. The switch from being quiet and inert to becoming active and dividing and spreading, may be influenced by a specific biologic process. We will use new drugs to target that process. These new drugs will be used to treat the cancer cells in the laboratory to find out if they can influence the switch between the quiet or inert cancer stem cell and the active cancer cell that multiply and grow faster. The student will work mostly in the laboratory, initially conducting preliminary work with cell lines but will also be involved with sample acquisition.

Contact supervisor: Dr. Mustafa Khasraw (Deakin Medical School): [email protected] 42152751 Suitable for: Honours

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56. Evaluation of new breast cancer drug Palbociclib in combination with radiation therapy Supervisor/s: Mustafa Khasraw, Andrea Muscat, Jason Hodge, David Ashley Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Several families of protein kinases orchestrate the complex events that drive the cell cycle, and their activity. This is frequently deregulated in cancer cells. Phosphorylation of the retinoblastoma protein, mediated by cyclin-dependent kinase 4 (CDK4) is required for entry of a cell into the cell cycle. The ability of cyclins to activate the cyclin-dependent kinases CDK4 and CDK6 is a documented mechanism of oncogenic actions and provides an attractive therapeutic target. Palbociclib is a novel inhibitor of both CDK4 and CDK6 kinase activity. Recent clinical studies with palbociclib have shown promise in the treatment of breast cancer and further reports indicate that it may also enhance radiation sensitivity in cancer cells, while at the same time imparting a radio-protective effect in normal cells. If this proves to be the case, palbociclib combined with radiotherapy will be an appealing approach against cancer.

The aim of this study is to measure the efficacy of palbociclib alone, and in combination with radiotherapy in both breast cancer cell lines and normal breast tissue with the hypothesis being that inhibition of CDK4/6 by palbociclib, given in combination with radiotherapy, will be protective to healthy cells but result in radio-sensitisation of cancer stem cells.

Contact supervisor: Dr. Mustafa Khasraw (Deakin Medical School): [email protected] 42152751 Suitable for: Honours

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57. Potential therapeutic use for a novel histone deacetylase inhibitor in paediatric solid tumours Supervisor/s: Jason Hodge, Sean McGee, Fiona Collier, David Ashley Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Heritable changes in gene expression that do not involve changes in DNA sequence are defined as epigenetics. One common mechanism of epigenetic regulation involves reversible histone acetylation. Cleavage of acetyl groups by histone deacetylases leads to a more condensed form of chromatin and gene silencing. Histone deacetylase inhibitors (HDACi) are a new class of anticancer drugs that cause changes in acetylation status that lead to alterations in gene expression, induction of apoptosis, cell cycle arrest, and inhibition of angiogenesis and metastasis in tumourigenic cells and solid tumours

We have developed a novel HDACi that binds specifically to the transcription factor myocyte enhancer factor-2 (MEF2), which was initially shown to be important in muscle differentiation, but also appears to play a key role in overall cellular differentiation. The aim of this study is to investigate the potential differentiative and/or apoptotic actions of this novel HDACi in tumourigenic cell lines derived from several paediatric solid tumours, including rhabdoid tumour, neuroblastoma and osteosarcoma. Together, these three tumours represent the most resistant of childhood cancers to current therapies and are the most devastating with regard to morbidity and mortality. The hypothesis of this study is that this novel HDACi will induce terminal differentiation and irreversible senescence in tumourigenic cells, with potential results warranting further investigation in in vivo models.

Contact supervisor: Dr. Jason Hodge (Deakin Medical School): [email protected] 52271174 Suitable for: Honours

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58. Genetic of tooth development in zebrfaih Supervisor/s: Yann Gibert Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Small variations in signaling pathways have been linked to phenotypic diversity and speciation. In vertebrates, teeth represent a reservoir of adaptive morphological structures that are prone to evolutionary change. Cyprinid fish, display an impressive diversity in tooth number and shape, but the signals that generate such diversity are unknown. Here, we show that retinoic acid (RA) availability influences tooth number size and shape in Cypriniformes. Heterozygous adult zebrafish heterozygous for cyp26b1 mutant which encodes an enzyme able to degrade RA possess an extra tooth in the ventral row. In contrast, increased RA levels generate longer teeth. Another Cypriniforme, Tanichthys albonubes with similarly long teeth was found to have delayed onset of cyp26b1 expression in the tooth-forming region. Our analysis suggests that changes in RA signaling play an important role in the diversification of teeth in Cypriniformes. Our work illustrates that, by being prone to heterochronic variations through subtle changes in the expression of rate-limiting enzymes, the RA pathway is an active player of tooth evolution in fish.

The Project will involve: • Pharmacological manipulation of pathways of interest in developing zebrafish, and phenotypic

characterization • Generation of inducible gain- or loss-of-function mutations in the zebrafish genome and phenotypic

characterisation • Immunohistochemistry, in situ hybridization • tooth staining Contact supervisor: Dr. Yann Gibert (Deakin Medical School): [email protected] 5227 1197 Suitable for: Honours

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59. The fate of Mesenchymal Stem Cells: how to get bone in zebrafish? Supervisor/s: Yann Gibert Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Age related osteoporosis is associated with an increase of adipose tissue and a reciprocal loss of bone density. Bones differentiate from a bone marrow-derived multipotent precursor cells: the Mesenchymal Stem Cells (MSCs). Differentiation of MSCs into osteoblasts is genetically driven. Recent studies have shown in zebrafish that normal expression of the Peroxisome proliferator-activator receptor gamma (Pparg) and retinoic acid (RA) is crucial for the proper balance of osteoblast differentiation. Furthermore membrane depolarization of human MSCs in vitro can prevent differentiation while hyperpolarization up-regulates osteogenic differentiation. However these results remain to be confirmed in vivo and during embryonic development. In this project we will characterize the precise developmental role of membrane potential changes on osteoblast differentiation using different molecular markers. Furthermore, the genetic cascade of MSC differentiation will be studied by abolishing and/or increasing candidate gene expression using specific pharmacological compounds, endocannbinoid signaling pathway. Once identified in zebrafish, the genes implicated in the fate of MSCs will be validated in a mammalian system to confirm their potential as therapeutic targets for osteoporosis. The Project will involve: • Pharmacological manipulation of pathways of interest in developing zebrafish, and phenotypic

characterization • Generation of inducible gain- or loss-of-function mutations in the zebrafish genome and phenotypic

characterisation • Immunohistochemistry, in situ hybridization • Bone staining • Quantitative RT-PCR from mammalian cells Contact supervisor: Dr. Yann Gibert (Deakin Medical School): [email protected] 5227 1197 Suitable for: Honours

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60. Microfluidics based circulating tumor cell (CTC) capture and analysis from patient samples Supervisor/s: Jagat Kanwar, Kislay Roy Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Use of circulating cancer cells (CTCs) as important marker for early cancer detection and diagnosis has received increased attention for the last few years. However, the rarity of occurrence of CTCs in peripheral blood samples (1-100 CTCs in 1 ml of blood) of cancer patients poses a major challenge in developing an efficient CTC detection platform. Therefore there is a need for development of simple easy-to-fabricate microfluidic devices that besides allowing high capture sensitivity and specificity also enable on-chip characterization of captured cells and subsequent release and culture of cells in vitro for further analysis. We have developed aptamer based micro-fluidic detection chips which can efficiently capture rare cells from a mixture containing a vast background of non-specific cells (cancer cells amongst healthy cells and RBCs). Besides the use for subsequent in vitro culture, these microfluidic devices also enabled on-chip characterization of captured cells for protein expression analysis for various stem cell markers. Apart from the very high binding specificity and immaculate sensitivity these aptamer-based detection chips can also be re-used for upto 10 times without any significant change in its sensitivity or specificity. We wish to move from in vitro cell detection to clinical samples in order to further validate the ability of our microfluidic devices. Use of aptamers as a more robust platform for CTC capture than antibodies is because of their increased thermal stability, resistance to degradation, ease of synthesis and strong binding to modified glass surfaces. Microfluidic devices modified with aptamers therefore offers a great potential in developing CTC capture devices that can be easily stored, transported and can be used for repeated analysis of several samples on the same device.


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61. Fat, muscle and cancer Supervisor/s: Julie Pasco, Sharon Brennan, Lana Williams, Kara Holloway Location: Barwon Health, Geelong Project description: This project is designed to explore the relationship between the amount and distribution of fat and muscle tissue in the body, and the risk of cancer. Detailed body composition data for men and women enrolled in the Geelong Osteoporosis Study will be linked with the Victorian cancer registry. While there are extant data that obesity increases cancer risk, research to-date has relied on anthropometric measures such as the body mass index (BMI, calculated from weight and height) or waist and hip circumferences. In this project the candidate will use dual energy x-ray absorptiometry (DXA) to more accurately measure body fat distribution and also determine total and appendicular muscle mass. This novel project will inform a growing awareness of a role for metabolically active tissue in the aetiology of cancer. Importantly, body composition may become recognised as a modifiable risk factor for cancer, and a potential target for prevention. The project will add to a growing evidence base for informing public health messages for the primary prevention of cancer. The candidate will work closely with the research team at the Epi-Centre for Healthy Ageing, in the Innovations in Mental and Physical Health and Clinical Trials Strategic Research Centre (IMPACT SRC), situated at Barwon Health. The project will foster an appreciation of epidemiological study design, data linkage and statistical analysis.

Contact supervisor: Prof. Julie Pasco (Deakin Medical School): [email protected] 61 3 4215 3331 Suitable for: Honours or PhD

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62. Developing aptamers into diagnostic tools Supervisor/s: Wei Duan, Sarah Shigdar Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: One of the first detectable signs of cancer progression and metastasis is the presence of circulating cancer cells in the blood. This indicates that a cancer is preparing to invade and colonise a secondary site, thus compromising organ function. Several methods have been developed to help enumerate these circulating tumour cells, including CellSearch, an FDA approved device for the detection of EpCAM positive cancer cells in the circulation. These devices currently use antibodies, which have several disadvantages. Our lab is focused on developing aptamers, chemical antibodies, which have been shown to be superior to conventional antibodies in a number of applications. We have developed aptamers targeted to several cancer-associated antigens including a number directed against EpCAM. This project will be focused on identifying the most accurate methods of identifying these circulating cancer cells, which antigens to target, and developing this into a diagnostic test that can be used in the future to aid oncologists in their treatment options, and therefore increase patient prognosis.

Contact supervisor: Prof. Wei Duan (Deakin Medical School): [email protected] 5227 1149 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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63. Targeting cancer with chemical antibodies Supervisor/s: Wei Duan, Sarah Shigdar Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Our laboratory is focused on developing a cure for cancer by targeting the cancer stem cells that hide and hibernate within the body, ready to spring back into action and cause recurrence or metastasis of the cancer. These cancer stem cells are refractory to traditional chemotherapy and require a more directed approach. We have been successful in developing chemical antibodies against two cancer stem cell markers, and will be adding to our repertoire in an attempt to eradicate cancer. These chemical antibodies, known as aptamers, are developed in the laboratory by a process known as SELEX, and can be directly linked to drugs, nanoparticles or radioisotopes. These smart bombs can target the tumourous tissues with high affinity and specificity, while leaving healthy tissue intact, thus minimising the toxic side effects of conventional treatment. The projects available will include the isolation and characterisation of RNA aptamers targeting a specific cancer associated cell surface marker, as well as investigating the possibility of linking several of our aptamers together in order to increase the effectiveness of our targeting system in a cancer cell model.

Contact supervisor: Prof. Wei Duan (Deakin Medical School): [email protected] 5227 1149 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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64. The quest for a biomarker of cancer cachexia Supervisor/s: Paul Lewandowski, Peter Martin Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: An estimated 50% of cancer patients develop skeletal muscle cachexia (wasting), suffering a significant loss of up to 30% of their original body weight. In addition when cancer patients develop cachexia they also have a decreased chance of survival and often must stop curative cancer therapies. Interestingly, research has shown that weight loss associated with cancer cachexia is not accounted for by a decrease in dietary intake, but rather a specific inflammatory catabolic response. Despite the prevalence of cancer cachexia, to date there is no cure or very few therapies that can slow or prevent the development of the condition.

Central to the treatment of cancer cachexia is the reliable diagnosis and prediction as to the rate at which the condition is likely to progress. To date there is no circulating factor that can be measured to predict or track the progression of cancer cachexia.

The aim of this project is to attempt to identify a novel blood biomarker that is associated with cancer cachexia. Given the recent advancement in diagnostic methods used ranging from measurement of circulating proteins to molecular genetic markers this project shall use a range of techniques to screen for potential biomarkers in the blood of patients and models of cancer cachexia.

Contact supervisor: Assoc. Prof. Paul Lewandowski (Deakin Medical School): [email protected] 03 52271111 Suitable for: Honours or PhD This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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65. Free living activity assessment of patients with cancer cachexia Supervisor/s: Paul Lewandowski, Peter Martin Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: An estimated 50% of cancer patients develop skeletal muscle cachexia (wasting), suffering a significant loss of up to 30% of their original body weight. In addition when cancer patients develop cachexia they also have a decreased chance of survival and often must stop curative cancer therapies. Interestingly, research has shown that weight loss associated with cancer cachexia is not accounted for by a decrease in dietary intake, but rather a specific inflammatory catabolic response. Despite the prevalence of cancer cachexia, to date there is no cure or very few therapies that can slow or prevent the development of the condition.

Resent investigations by A/Prof Lewandowski and Martin's research group has suggested that maintaining physical activity may be beneficial in the treatment of cancer cachexia. The limitation to the research in this area to date is that all data has been collected in a clinical setting and not the patients home.

The current project aims to use portable accelerometer technology together with traditional measures of activity and lifestyle to: 1) Measure the activity levels of patients with cachexia during their normal daily activities. 2) Use the same techniques to monitor the effect of a lifestyle intervention on physical activity levels and patient outcomes.


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66. Novel treatments of cancer cachexia Supervisor/s: Paul Lewandowski, Melanie Sullivan-Gunn Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: An estimated 50% of cancer patients develop skeletal muscle cachexia (wasting), suffering a significant loss of up to 30% of their original body weight. In addition when cancer patients develop cachexia they also have a decreased chance of survival and often must stop curative cancer therapies. Interestingly, research has shown that weight loss associated with cancer cachexia is not accounted for by a decrease in dietary intake, but rather a specific inflammatory catabolic response. Despite the prevalence of cancer cachexia, to date there is no cure or very few therapies that can slow or prevent the development of the condition. In this project novel nutritional, life style or drug therapies will be tested in an attempt to treat cancer cachexia.

This project will provide students with the opportunity to learn clinical trial experience, animal surgical techniques, cell culture and skills needed to run a dietary trial. In addition the project also incorporates Gene expression analysis, protein electrophoresis & immunoblotting, biochemical analysis, enzymatic analysis and histological analysis.


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67. The role of free radicals in the development of cancer cachexia Supervisor/s: Paul Lewandowski, Melanie Sullivan-Gunn Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: An estimated 50% of cancer patients develop skeletal muscle cachexia (wasting), suffering a significant loss of up to 30% of their original body weight. In addition when cancer patients develop cachexia they also have a decreased chance of survival. Interestingly, research has shown that weight loss associated with cancer cachexia is not accounted for by a decrease in dietary intake, but rather a specific inflammatory catabolic response. Free radicals have been suggested to contribute to progressive tissue damage in other diseases of heart muscle, kidney, spinal cord, vascular smooth muscle and skeletal muscle, but to date the role of free radicals in the development of cancer cachexia has not been studied. To study cancer cachexia A/Prof. Lewandowski’s laboratory has developed a number of novel models that they employ to study the development of the disease and its treatment.

This project will provide students with the opportunity to learn cell culture techniques and skills needed to run a dietary trial. In addition the project also incorporates gene expression analysis, protein electrophoresis & immunoblotting, biochemical analysis, enzymatic analysis and histological analysis.

Contact supervisor: Assoc. Prof. Paul Lewandowski (Deakin Medical School): [email protected] 03 52271111 Suitable for: Honours or PhD

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68. Chemokine signalling, bone marrow derived endothelial progenitor cells (EPCs) and cancer. Supervisor/s: Albert Mellick, Prue Plummer Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Survival of tumour cells is contingent upon evasion of the host immune response and recruitment of a range of cell types that cooperatively ensure survival of the tumour organ. Bone marrow-derived endothelial progenitor cells (EPCs) are among the earliest cells involved in angiogenesis. Work by our laboratory has shown that blocking EPC recruitment can dramatically effect tumour and metastatic growth. Inhibitor of DNA binding 1 (Id1) is a transcription factor that has been shown to be over-regulated in a range of cancers and may be a marker for malignant potential. Id1 also has been shown to mark EPCs as they incorporate into nascent vasculature. Loss of Id1 expression significantly impairs angiogenesis and tumour growth. Thus, a complex interplay of signalling molecules from both tumour and stromal cells drives the angiogenic switch. The inflammatory cytokine chemokine ligand 5 (CCL5) and its receptor CCR5, are strongly up-regulated in the tumour environment. By using lentiviral delivery of shRNA targeting Id1, CCL5 and CCR5 in the 4T1 mouse breast cancer cell line, we aim to elucidate the effects of these molecules on angiogenesis and the bone marrow recruitment of EPCs.

The aims of this project are to: 1) Determine the role of chemokine receptors in EPC mediated tumour growth and angiogenesis 2) Determine the role of chemokine receptors in EPC mediated metastasis 3) To target chemokine receptors in vivo in a mouse tumour model for therapeutic effect. This project will involve: quantitative-PCR, cell culture, RNA extraction, FACS analysis, mouse work and cloning.

Contact supervisor: Dr. Albert Mellick (Deakin Medical School): [email protected] 0352272845 Suitable for: Honours or PhD

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69. Identification and functional validation of downstream targets of cancer microRNAs. Supervisor/s: Albert Mellick, Prue Plummer Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: MicroRNAs (miRNAs/miRs) are small-noncoding RNAs (of about 18-23bp) that regulate a range of development and disease processes. At a post transcriptional level they regulate signalling pathways controlling all aspects of cell biology, including cell growth, death and differentiation. Furthermore, they play a particularly important role in stem cell differentiation in a range of organs, including the vascular compartment. Bone marrow derived endothelial progenitor cells (EPCs) are critical to tumour angiogenesis, growth and metastasis.

In 2013, the Mellick lab showed that miRNAs were required for EPC biology (Plummer et al., Cancer Research 2013;73:341-52). Using Small RNA Illumina Sequencing and Quantitative-PCR validation several candidate miRNAs were identified, including miR-10b and miR-196b. We also showed Homeobox D10 (HOXD10) is a downstream target of miR-10b and that the regulation of HOXD10 is critical to EPC biology and tumour growth. However, all of the downstream targets of miR-10b and miR-196b are not known. As RNA based therapies are being developed to suppress microRNAs this presents a significant problem as the effect of such therapies on downstream pathways are unknown. The focus of this project is to identify downstream targets of miR-10b and miR-196b and functionally validate these targets.

The aims of this project are: 1) Identify the potential downstream targets of these microRNAs using bioinformatics prediction programs 2) To functionally validate these targets using in vitro angiogenesis assays 3) To functionally validate these targets in vivo using tumour (breast cancer) and angiogenesis assays. This project involves: quantitative-PCR, cell culture, RNA extraction, FACS analysis, mouse work including tumour growth and injections, Fluorescent locked nucleic acid in-situ hybridization and microscopy.


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70. Specific Targeting of MicroRNAs as a Novel Anti-Cancer Therapy. Supervisor/s: Albert Mellick, Prue Plummer Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Angiogenesis is critical for the growth of new vessels in tumours. The Mellick Lab and others have demonstrated that bone marrow derived endothelial progenitor cells (EPCs) are critical to this process. Small non-coding microRNAs (miRNAs) are key players in cellular differentiation; that represent a newly discovered mechanism for gene regulation. The Mellick Lab has recently published in Cancer Research (Plummer et al., 2013. 73:341-52) work showing that angiogenesis linked microRNAs can be suppressed in vivo resulting in a significant decrease in tumour growth and blood vessel development. This project focuses on developing this novel technology, to be able to specifically target bone marrow EPCs and thus target tumour growth without side-effects associated with current anti-angiogenesis therapy which also target normal vasculature.

The aims of this project are: 1) To specially target EPC microRNAs in vivo using EPC peptide liposomal delivery system encapsulating anti-miRNAs 2) To determine the effect of this novel treatment in vivo on tumour growth (breast cancer) and angiogenesis 3) To determine the correct dose of anti-miRNAs to have a biological effect. The project will involve: quantitative-PCR, cell culture, RNA extraction, FACS analysis, mouse work including tumour growth and injections, fluorescent locked nucleic acid in-situ hybridization and microscopy.


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Nutrition, Bone Health

71. Can histone deacetylase inhibitors stimulate bone formation? Supervisor/s: Jason Hodge, Sean McGee, Fiona Collier, David Ashley Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Pathological bone loss is associated with many common diseases including osteoporosis, metastatic diseases of bone and rheumatoid arthritis. Bone homeostasis is maintained by a process called remodeling, which involves the tight coupling of bone resorption, performed by osteoclasts (OC), with subsequent bone formation performed by osteoblasts (OB). This coupling is essential for the correct function and maintenance of the skeletal system, repairing microscopic skeletal damage and replacing aged bone. A disruption of normal bone remodeling, with enhanced bone resorption by OC is a characteristic feature of the above diseases and hence factors that reduce OC resorption have become important targets for therapeutic intervention. Relatively few therapeutic options exist, however, that succeed in promoting bone formation by OB. Histone deacetylase inhibitors (HDACi) are a new class of anticancer drugs that cause changes in histone acetylation status, which lead to alterations in gene expression, induction of apoptosis, cell cycle arrest, and inhibition of angiogenesis and metastasis in tumourigenic cells and solid tumours. Recent studies have demonstrated that both OC and OB express HDACs and that targeting of specific HDACs with HDACi can both suppress OC formation and resorption, and promote OB maturation and mineralization, both in vitro and in vivo. We have developed a novel HDACi that binds specifically to the transcription factor, myocyte enhancer factor-2 (MEF2), which has recently been implicated in OB differentiation and maintenance of bone mass. The aim of this study is to investigate the actions of this novel HDACi in human in vitro models of OC and OB formation and function. The hypothesis to be tested is that the HDACi will stimulate OB differentiation and bone mineralization, but inhibit osteoclastogenesis.

Contact supervisor: Dr. Jason Hodge (Deakin Medical School): [email protected] 52271174 Suitable for: Honours This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

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72. Identifying the role of miRNA in the development and regulation of inflammatory rheumatic diseases

Supervisor/s: Jagat Kanwar, Rasika Samarasinghe, Rupinder Kanwar Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: There are over 100 different forms of rheumatic diseases affecting over 4% of the population worldwide. Among these, the most widespread conditions that cause severe pain, inflammation and permanent disability are rheumatoid arthritis (RA) and osteoarthritis (OA). Although the exact etiology of RA and OA remains unknown, growing evidence has revealed the dysregulation of microRNAs (miRNAs) in rheumatic patients may contribute to molecular activation and disease progression. miRNAs, small RNAs of 21-25 nucleotides, play a critical role in the molecular process of cells. They have a direct influence on the regulation of mRNA expression leading to the cleavage and repression of disease inducing mRNA activity. On the other hand, dysregulation of miRNA may also amplify the pathogenesis of rheumatic disease. Therefore, a better understanding of the pathophysiological role of miRNA in RA and OA is imperative.

This project aims to further our understanding of the regulation of miRNA in the development of arthritic diseases. The expression of miRNA will be elucidated in articular cartilage cells and in immune cells when exposed to different physiological conditions, as well as examining how these changes lead to alterations in signalling mechanisms associated with arthritis. This approach will offer an in depth insight into the pathogenesis of disease as well as the development of potential therapeutics for the treatment of inflammatory rheumatic diseases.


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73. Childhood asthma and the risk of fracture Supervisor/s: Sharon Brennan, Julie Pasco, Lana Williams, Kara Holloway Location: Barwon Health, Geelong Project description: There are a number of reasons children with asthma may be more susceptible to fracture, which include the use of beta agonists and corticosteroid medications, differences in activity levels and the disease process itself. However, these associations have not yet been examined for the Geelong and surrounding districts. The aim of this study is to compare fracture rates in children with and without asthma. In 2005, the Geelong Childhood Asthma Study identified a community-based sample of primary school aged children with asthma. Incident fracture cases will be identified from radiology reports that are collated to form a comprehensive fracture register for our region. Fracture rates in children identified as having asthma will be compared with fracture rates from the general community of primary school aged children that do not have asthma. The project will foster an appreciation of epidemiological study design, data linkage and statistical analysis. This project presents the opportunity to utilize good quality data from two large community-based projects to generate clinically useful information. This is a collaborative project between the Geelong Osteoporosis Study and Dr Peter Vuillermin, Paediatrician. The candidate will work closely with the research team at the Epi-Centre for Healthy Ageing, in the Innovations in Mental and Physical Health and Clinical Trials Strategic Research Centre (IMPACT SRC), situated at Barwon Health.

Contact supervisor: Dr. Sharon Brennan (Deakin Medical School): [email protected] 61 3 4215 3334 Suitable for: Honours or PhD

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74. Sarcopenia and nutritional risk, falls and functional mobility Supervisor/s: Julie Pasco, Sharon Brennan, Lana Williams, Kara Holloway Location: Barwon Health, Geelong Project description: There is great diversity in the health and wellbeing of the elderly population. Changes in nutritional status and body composition affect disease risk and quality of life, and can influence the need for aged-care. This project will focus on components of sarcopenia (age-related muscle wasting and muscle weakness) that are key determinants of falls, functional mobility and independence. There is a gap in knowledge about how malnutrition impacts on age-related muscle deterioration and the sequelae of this decline in our region. This project will inform the evidence base for preventing disability associated with the onset and progression of frailty, and sustaining independence and good quality of life.

This quantitative project involves new and existing data from participants of the Geelong Osteoporosis Study. During data collection, analysis and interpretation, the candidate will work closely with the research team at the Epi-Centre for Healthy Ageing, in the Innovations in Mental and Physical Health and Clinical Trials Strategic Research Centre (IMPACT SRC), situated at Barwon Health.


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75. The epidemiology of limb fractures Supervisor/s: Kara Holloway, Julie Pasco, Sharon Brennan, Lana Williams Location: Barwon Health, Geelong Project description: Fractures of the scaphoid, foot and ankle are examples of common limb fractures; however, little is known about their epidemiology, risk factors or association with morbidity and mortality. This is surprising given that these fractures often have a poor prognosis and can have a substantial impact on quality of life. Furthermore, as limb fracture patients often have co-morbid conditions, treatment can be complex. The candidate working on this project will describe the epidemiology of these fractures and fulfil a major public health goal to identify specific risk factors for these limb fractures. Incident fracture cases will be identified from radiology reports that are collated to form a comprehensive fracture register for our region. Using a nested case-control study design the candidate will use data from the Geelong Osteoporosis Study to compare and contrast fracture cases with non-fracture controls to identify risk factors for fracture. Potential clinical risk factors include bone mineral density, heel ultrasound, anthropometry, body composition, blood pressure, diet, alcohol consumption, physical activity, and exposure to medications and diseases. Post-fracture morbidity and mortality data will also be used to determine the long-term impact of these fractures. The project will be conducted at the Epi-Centre for Healthy Ageing, in the Innovations in Mental and Physical Health and Clinical Trials Strategic Research Centre (IMPACT SRC), situated at Barwon Health.

Contact supervisor: Dr. Kara Holloway (Deakin Medical School): [email protected] 3 4215 3332 Suitable for: Honours or PhD

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76. Food outlet space allocated for fruit and vegetables and health status in Australian farmers? Supervisor/s: Paul Lewandowski, Colin Bell, Scott McCoombe Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Dietary patterns may be influenced by the availability and accessibility within shops/stores of different types of foods. In urban areas it has been shown that measurements of shelf space devoted to the sale of items such as fruit and vegetables can be used by researchers to characterize the healthfulness of the food environment. However, little is known about the amount of shelf space used for healthy and unhealthy foods in different types of shops/stores in rural areas and how this relates to the health of individuals who shop there.

This project will provide students with the opportunity to travel throughout Victoria to survey the range of foods available for sale in regional supermarkets and other food outlets. This will involve collecting in store food inventories, measurements of space allocated to different foods, collection of diet diaries, carrying out food frequency surveys and data analysis. Students would be expected to spend up to 1 week per month over a 5-month period collecting data in the field, would have access to a car and support to cover over travel expenses.

Contact supervisor: Assoc. Prof. Paul Lewandowski (Deakin Medical School): [email protected] 03 52271111 Suitable for: PhD

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77. Bone mineral density in monoclonal gammopathy of uncertain significance (MGUS) Supervisor/s: Mark Kotowicz, David Ashley Location: Barwon Health, Geelong Project description: Monoclonal gammopathy of uncertain significance (MGUS) is a precursor of multiple myeloma with approximately 1% of case progressing to multiple myeloma each year. Multiple myeloma is frequently complicated by osteoporosis and fragility fractures, secondary to the abnormal plasma cell’s production of bone-resorbing cytokines, with skeletal related events causing significant morbidity. Much less is known about the skeletal outcomes of MGUS. Case-control studies have shown an increase in fracture risk among MGUS patients. Whether the increase in fracture risk is related to reduced bone mass, microarchitectural deterioration of the skeleton or alterations in bone turnover is unknown.

This project will examine bone mineral density (BMD) in MGUS patients, recruited from the haematology clinic at Barwon Health and compare BMD with age- and sex-matched controls drawn from the Geelong Osteoporosis Study age-stratified, population-based random samples. The student will recruit participants, obtain informed consent, schedule appointments, administer questionnaires collate and analyse data. Contact supervisor: Assoc. Prof. Mark Kotowicz (Barwon Health): [email protected] 03 4215 2899 Suitable for: Honours This project is subject to final approvals.

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78. Determining trends in diet quality over the long term Supervisor/s: Felice Jacka, Julie Pasco, Adrienne O'Neil Location: Barwon Health, Geelong Project description: This project takes place in the setting of a large ongoing cohort study of women. The project entails a detailed investigation of dietary intakes in women participating in the ongoing Geelong Osteoporosis Study (GOS), which comprises a sample of nearly 1000 women from across the adult age range. The project will involve a validation of the initial technique used for estimating dietary intakes from food diaries and a further assessment of dietary intakes and how they vary or otherwise over 15 years of follow up. Understanding the trajectory of diet quality and its stability or otherwise is very important in extrapolating findings from observational studies.

The student will be based in Geelong and co-supervised by Professor Julie Pasco. Students will gain hands on experience in data analysis and have exposure to a wide range of research projects being undertaken in the setting of the IMPACT SRC. This project would ideally suit those with a psychology or a nutrition background.


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79. Are medical students healthy? An assessment of chronic disease factor prevalence Supervisor/s: Colin Bell, Scott Mccoombe, Erik Martin

Location: School of Medicine, Deakin University, Waurn Ponds Campus

Project description: Chronic diseases such as cardiovascular disease, diabetes, chronic respiratory diseases and cancer are the leading causes of illness and death in Australia and health professionals are not spared. Given their youthfulness, medical training and interest in health, it is reasonable to assume that medical students have healthy diets, are physically active, don't smoke and use alcohol responsibly, placing them at low risk of chronic disease. However, the sedentary nature of their training and the stress associated with performing well in a demanding and fast-tracked medical course may increase their risk.

Using recognised surveillance tools and techniques, dietary, physical activity, tobacco and alcohol related behaviours will be assessed by online questionnaire. Weight, height, waist circumference and blood pressure will also be assessed along with fasting blood glucose and total and HDL cholesterol using capillary blood from a finger prick.

This project will shed light on chronic disease risk in a cross-section of approximately 135 medical students at Deakin University. It will also shed light on whether awareness of chronic disease risk at a young age is likely to stimulate behaviour change.

Contact supervisor: Assoc. Prof. Colin Bell (Deakin Medical School): [email protected] 52278043 Suitable for: Honours

This project involves the handling of human blood and bodily substances, any student undertaking this project will be advised by the Principal Investigator to review your vaccination history and immune status.

This project is subject to final approvals.

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Other

80. Action of Dopamine and antipsychotics on bone formation, in zebrafish Supervisor/s: Yann Gibert, Lana Williams, Daniel Fraher Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Antipsychotics are amongst the most commonly used medications, and their use for schizophrenia and related conditions tends to commence in early adulthood and be lifelong. Both dopamine (DA) and antipsychotics affect bone metabolism. In one study, DA-transporter (DAT)-deficient mice displayed a low bone mass phenotype. However their role during bone formation is still unknown.

This project will investigate the effects of DA and selected antipsychotics on bone development during zebrafish embryogenesis. At the time of bone induction, at 48 hours post fertilization (hpf) zebrafish embryos will be exposed to DA, and selected antipsychotics until fixation at 72, 96 hpf or 5.5 days pf (dpf). Resulting phenotype on bone development will be monitor by Alizarin red staining for mineralised tissue, alkaline phosphatase for osteoblast lineage. All staining will be performed at 5.5 dpf. Expression of several genes markers of bone development will be investigated by whole mount in situ hybridisation (WISH): runx2a and runx2b (for osteoprogenitor cells), osterix and osteocalcin (for differentiating osteoblast), alkaline phosphatase, and colagen10a1 (for mature osteoblast) and matrix metalloproteinase 9 (for osteoclast lineage). WISH will be performed at 72 or 96 hpf depending of the probe used. This project will definitively linked dopamine and antipsychotic and bore formation in vertebrates.

The Project will involve: • Pharmacological treatments of zebrafish embryos and phenotypic characterization • Bone staining • Immunohistochemistry, in situ hybridization

Contact supervisor: Dr. Yann Gibert (Deakin Medical School): [email protected] 5227 1197 Suitable for: Honours

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81. Cage, barn or free range? Which system has the happiest chicken? Supervisor/s: Tamsyn Crowley, Anthony Keyburn Location: School of Medicine, Deakin University, Waurn Ponds Campus Project description: Heavily driven by public perception and large supermarket monopolies, welfare is of major concern for the poultry industry. The past few decades has seen development of poultry practices with a heavy focus on the welfare of poultry. There have been huge changes implemented to accommodate improvements in welfare particularly in the layer industry. There are now a number of production systems including caged and free range which provide the consumer a conscious choice on how their eggs have been produced. While these developments have undoubtedly facilitated an increase in perceived welfare standards there is little research to confirm that there has been an actual increase in welfare standards and reduced stress on the birds. Many of the demands placed on the industry in terms of welfare are essentially based on public perception and interpretation, thus making it difficult to objectively assess the real welfare situation. Currently there are a number of behavioural and biochemical tests (corticosterone levels) that have provided an insight into the welfare of poultry, but to date there is no clear scientific test that can be attributed to welfare. This project will develop a clear cut test that will determine the welfare/stress on layers in various production systems. This will enable the industry to provide accurate scientific information on the welfare status of their production systems. This test will also enable auditors to directly test welfare during the course of their routine inspections. The aim of this project is to develop an evidence based diagnostic test for welfare. The test will determine a bird’s state of welfare by looking at its microRNA profile. We will work closely with existing Poultry CRC welfare projects and industry to develop a commercially viable end user product.

Contact supervisor: Dr. Tamsyn Crowley (Deakin Medical School): [email protected] 61352271328 Suitable for: Honours or PhD

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82. Ageing, chronic disease and quality of life Supervisor/s: Sharon Brennan, Julie Pasco, Lana Williams, Kara Holloway Location: Barwon Health, Geelong Project description: Quality of life (QoL) is a broad and multifactorial construct. The fundamental right of every individual is to enjoy the highest attainable standard of wellbeing and health, however this ability is influenced by age, sex, physical capabilities, disease and social and personal resources. This project is designed to investigate the relationship between ageing, chronic disease/s and QOL among men and women enrolled in the Geelong Osteoporosis Study The student will measure QoL by questionnaire using a country-specific validated World Health Organisation (WHO) QoL tool. Data pertaining to chronic disease will be ascertained from a combination of clinical measurements, medical histories and self-reported information. The student will learn and employ regression techniques to determine associations between age, chronic disease and QoL in the four psychosocial domains of physical, mental, social and environment. This project will be undertaken within the newly formed Social Epidemiology branch of the Epi-Centre for Healthy Ageing, located in the IMPACT SRC (Innovations in Mental and Physical Health and Clinical Trials).

Contact supervisor: Dr. Sharon Brennan (Deakin Medical School): [email protected] 61 3 4215 3334 Suitable for: Honours or PhD

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83. Modifiable risk factors for chronic disease: a population-based study Supervisor/s: Julie Pasco, Sharon Brennan, Lana Williams, Kara Holloway Location: Barwon Health, Geelong Project description: Project description: The burden of chronic disease in Australia is poised to escalate as life expectancy increases and the population ages. It is of great public health importance to promote healthy ageing and minimise risk profiles for chronic diseases at a population level. This project will utilise data from the Geelong Osteoporosis Study to focus on building an evidence base for our region that describes the prevalence of modifiable risk factors thereby identifying targets for intervention. Potential targets include smoking, alcohol abuse, physical inactivity, poor diet, malnutrition, hypertension and obesity.

The candidate will work closely with the research team at the Epi-Centre for Healthy Ageing, in the Innovations in Mental and Physical Health and Clinical Trials Strategic Research Centre (IMPACT SRC), situated at Barwon Health. The project will foster an appreciation of epidemiological study design, sampling techniques, participant-researcher interaction, database design and management, and statistical analysis.


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84. Are there gender differences in food consumption patterns by individuals with major depression

Supervisor/s: Felice Jacka, Adrienne O'Neil Location: Barwon Health, Geelong Project description: We are conducting a Randomised Controlled Trial (RCT) to investigate the efficacy of dietary improvement as a treatment strategy for Major Depressive Disorder. This trial is based in Melbourne; however, the project can be co-based in Geelong. It is important to understand the potentially differential impact of depression on dietary habits. This project will investigate gender differences between individuals participating in the trial. We want to know which gender has poorer quality diets. Moreover, we would like to investigate whether there are gender differences regarding foods selected as a result of experiencing depression / anxiety (e.g. do women crave sugars, whereas men crave chips and fatty snacks? Do women still eat more vegetables than men when depressed?). Dietary intakes and quality will be measured using a validated FFQ and algorithm, as well as gold-standard food diaries. Data will be drawn from the baseline questionnaires completed by trial participants. As well as supervision from senior academic staff, students will receive support from qualified dietitians in this undertaking. They will gain valuable hands-on experience of research in the context of a randomised controlled trial. This project would ideally suit those with a psychology or a nutrition background.


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85. Does participation in the control group of a health intervention prompt changes in health behaviour?

Supervisor/s: Felice Jacka, Adrienne O'Neil Location: Barwon Health, Geelong Project description: We are conducting a Randomised Controlled Trial (RCT) to investigate the efficacy of dietary improvement as a treatment strategy for Major Depressive Disorder. This trial is based in Melbourne; however, the project can be co-based in Geelong. Sometimes participation in an intervention that is focused on lifestyle behavioural change can prompt people to make changes in their behaviours, even when they are not in the intervention itself. This is very important to map, as it can obscure the impact of the intervention on the outcomes. This project will investigate whether the diets of participants in the social support control group of an the RCT change between baseline and end assessment as a function of participation in the trial. Dietary intakes and quality will be measured using a validated FFQ and algorithm. Data will be drawn from a subgroup of trial participants. As well as supervision from senior academic staff, students will receive support from qualified dietitians in this undertaking. They will gain valuable hands-on experience of research in the context of a randomised controlled trial. This project would ideally suit those with a psychology or a nutrition background.


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